TAG: "Eye care"

UC Grad Slam winners make research accessible one pitch at a time

Graduate students captivate audience by keeping it simple.

UC Irvine's Ashley Fong delivers the top-prize-winning presentation at the UC Grad Slam on using stem cells to mend damaged hearts. (Photos by Robert Durell)

By Nicole Freeling

>>Watch UC Grad Slam and individual students’ presentations

It took UC Irvine graduate student Ashley Fong years to make significant advances in her research using stem cells to repair damaged heart muscle, but just minutes — three to be exact — to wow a panel of judges with a succinct explanation of her work and capture the championship at the first UC-wide Grad Slam tournament.

Graduate students are rarely rewarded for being brief or simple, but those were the exact requirements to win Monday, as 10 UC scientists and scholars competed to deliver the most illuminating three-minute explanation of their work.

An elated Fong took home $6,000 in prize money and the glory of out-talking her peers — all of whom had won similar contests at their home campuses and provided some tough competition.

Coming in second and third place were Daniel Hieber of UC Santa Barbara and Alex Phan of UC San Diego, with talks on efforts to save a language from extinction and a device to help glaucoma patients.

“I have experience speaking at conferences,” Fong said. “But those are long talks, with dozens of slides, to a roomful of experts.”

She participated in Grad Slam, she said, to learn to communicate her work and why it matters to people outside the field. That skill is a growing necessity for researchers everywhere, as public funding for research and higher education grows ever more competitive. In such a climate, academics who can articulate the value of their research have an important edge. Grad Slam was aimed at giving master’s and Ph.D. students important career-building skills, while offering the public a window into the breadth of work being done across UC campuses.

Contestants spent weeks preparing, taking workshops and working one-on-one with coaches to hone their ideas, craft the structure of their talk and present extremely complex ideas in a way that would be relatable to a general audience.

By the time they took to the stage Monday, the students had honed their presentations to a fine point. Most were also well-versed in speaking in front of an audience, having competed in several qualifying rounds before taking the top prize on each of their campuses.

Public speaking did not come naturally at first, said Phan, a graduate student in mechanical and aerospace engineering. “But once you take this on, it stops being quite so uncomfortable. You begin to build up your confidence.”

The effort paid off: Phan won third place for his talk Fight for Sight, about an implantable pressure sensor that provides continuous monitoring for glaucoma patients. Phan ultimately hopes to patent the technology and bring it to market. When the award was announced, Phan’s parents, who had traveled from Los Angeles to watch the competition, leapt from their seats. “We are so proud of him,” said his mother.

UC Grad Slam winners Alex Phan, left, third place; Ashley Fong, first place; and Daniel Hieber, second place.

Learning to demystify their research

“Making the mysteries of basic research more understandable and accessible to the public is one of my priorities, and part of our responsibility as the nation’s premier public research university,” said UC President Janet Napolitano, who served as the event emcee. “Grad Slam plays a key role in highlighting the broad, societal significance of research at UC.”

Non-academics, including NBC Bay Area News anchor Jessica Aguirre, Silicon Valley venture capitalist Josh Green and Oakland Mayor Libby Schaaf, joined UC Regent Eddie Island and UC Provost Aimée Dorr as the contest judges. They evaluated contestants based on their ability to clearly and concisely explain their research and its impact.

The judges had a difficult task in determining the winner from a field of students, all of whom came across as polished, engaging and passionate about their pursuits.

“It’s been so great to be able to explain my research to people in my church, to my friends,” said UCLA master’s student Jean Paul Santos, who told the audience about a small, more powerful antennae he is engineering to help NASA scientists communicate directly with the Mars rover. “I had to figure out, how can I share the novelties of my research without going overboard or over your head?”

UC Riverside plant pathologist Jeannette Rapicavoli, who is a first-generation college student, said the experience had helped her better explain her research to her family. “It was like: ‘So this is why you want to be in college for nine years. We can understand it now.’”

Students described new insights into how species behave, how to help crops withstand drought, and how food waste can be harnessed as a source of fuel.

Reviving a dead language

Daniel Hieber, a linguistics Ph.D. student and the lone competitor not in a science, technology or engineering field, took second place for his talk about how he has helped to revive a language in the Louisiana bayou whose last native speakers died in the 1930s. From wax audio recordings of their voices, along with written archives, Hieber has reconstructed the Chitimacha language, even creating a Rosetta Stone audio tape, which tribal members now listen to in their cars.

“For the first time in 70 years, you can hear Chitimacha being spoken again in the schools and communities of the bayou,” Hieber said.

Following each of the presentations, Napolitano bantered with researchers, asking them about how they got interested in their line of research. “The work you’re doing represents years of serious research. But there’s no reason we can’t have a little fun,” she said.

UC Davis food scientist Ryan Dowdy described how as a boy, he would mix together water, oil and food coloring as a kid and sell it on the street, instead of the usual lemonade.

“I charged 50 cents. I made a killing.”

Dowdy and his peers represent an emerging breed of researchers, who are breaking down the stereotype of the elite intellectual, said National Public Radio contributor Sandra Tsing Loh, who teaches a science communications class at UC Irvine and had come to cheer contestants on. The public is hungry, Lo said, for scholars and scientists who can unleash the excitement of their discoveries.

Far from fitting the image of the aloof scientist, Grad Slam contestants described their passion pursuing advances that directly touch the lives of Californians and people elsewhere.

Fong described the mantra she uses when the rigors and frustrations of research overwhelm her. It was the same one she used at Grad Slam to get herself primed for the competition. “When I need to ground myself, I just remember, I want to save lives. That’s the reason I got into research.”

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Study sheds new light on low-light vision

Brain handles day- and nighttime optical signals the same, reacts quickly to loss of input.

Alyssa Brewer, UC Irvine

By Heather Ashbach, UC Irvine

Driving down a dimly lit road at midnight can tax even those with 20/20 vision, but according to a recent UC Irvine study, the brain processes the experience no differently than if it were noon. The same study also reveals how quickly the brain adapts to vision loss, contradicting earlier research and opening the door to novel treatments.

The findings, which appear in the April 21 edition of Proceedings of the National Academy of Sciences, are significant for those who have suffered retinal damage or disease, said cognitive scientist Alyssa Brewer, the lead author.

“Previous research suggested that the two areas of the brain responsible for color processing received input only from cone photoreceptors – the parts of the retina used in central, normal daylight vision for things like reading and seeing details and colors in a scene,” she said.

However, Brewer and co-author Brian Barton, a postdoctoral researcher in cognitive sciences, employed functional MRI to determine that rod photoreceptors, which are only active under very low light, also play a role in the color experience and use the same neural pathways that cones do.

“This is surprising because there are no rods in the central part of the retina, the part we use to see fine details,” Brewer said. “We are functionally blind in the center of our vision under low light, something we call a ‘rod scotoma.’”

To compensate for this vision loss, people look at objects under low light at an angle that accesses the rod receptors.

This adaptation gives researchers an opportunity to track how the brain responds to what the eye sees without using central vision – similar to the way individuals with retinal damage interpret what they see.

Brewer and Barton had test subjects sit in a completely dark room for 30 minutes and then view checkerboard stimuli under very low light while their brain activity was measured with fMRI. In addition to the neural pathway finding, they discovered that the brain adapts immediately to required shifts in vision – a process previous work had said could take months.

“The amount and timing of the brain’s ability to reorganize to compensate for a loss of visual input is very important for us to understand what types of rehabilitation can help recovery,” Brewer said. “The temporary and reversible rod scotoma from low-light conditions provides an excellent way for us to study how the brain reacts and recovers from vision loss, something we found to be immediate rather than long-term.”

“By being able to accurately track how the brain responds to retinal damage, we can begin to create new rehabilitation techniques that could help restore vision,” she added.

The study is available online at www.pnas.org/content/early/2015/04/01/1423673112.full.pdf.

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FDA greenlights clinical trial of treatment for blinding disease

Novel retinitis pigmentosa therapy created by UC Irvine stem cell researchers.

UC Irvine professor Henry Klassen is using stem cells to cure retinitis pigmentosa. (Photo by Steve Zylius, UC Irvine)

A first-of-its-kind stem cell-based treatment for retinitis pigmentosa developed by UC Irvine’s Dr. Henry Klassen, Dr. Jing Yang and colleagues has received consent from the U.S. Food & Drug Administration for use in a clinical trial.

A startup co-founded by Klassen and Yang to commercialize the therapy, jCyte Inc., will administer the trial – the first to be held at UCI to test a remedy created by UCI stem cell researchers. The investigational treatment is intended to preserve vision by intervening at a time when degenerating photoreceptors (rods and cones) can be protected and potentially reactivated.

“This milestone is a very important one for our project,” said Klassen, an associate professor of ophthalmology affiliated with UCI’s Sue & Bill Gross Stem Cell Research Center and Gavin Herbert Eye Institute. “It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this progress.”

By midyear, the phase one/two study will begin enrolling up to 16 patients at UCI and a possible second site. The primary purpose of the trial is to determine the safety of a single injection of retinal progenitor cells into the eyes of patients with advanced retinitis pigmentosa. But the effect on ocular function also will be assessed.

Stem cell therapy offers a new and promising approach to devastating blinding diseases such as RP, for which there is no current treatment. The initiation of this clinical trial represents the culmination of a research project stretching back more than a decade – a project, according to Klassen, accelerated by support from the state’s stem cell agency, the California Institute for Regenerative Medicine, which was created when voters passed Proposition 71 in 2004.

“Without the backing of CIRM and the people of California, we would have never made it this far this quickly,” Klassen said. “To the patients and their families who have been waiting all these years, I am delighted to finally be taking our research out of the lab and into the clinic.”

CIRM has granted the team $21 million to date for the project. While the funding is extremely important, Klassen stressed that the agency also tutors and guides its grantees in the many aspects of translational development and that this partnership grows closer during the later preclinical phase, where much is at stake.

“One of CIRM’s goals is to provide the support that promising therapies need to progress and ultimately get into clinical trials with patients,” said Jonathan Thomas, Ph.D., J.D., chair of the agency’s governing board. “RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Sidney Golub, director of UCI’s Sue & Bill Gross Stem Cell Research Center, added: “We are thrilled that this trial is on the verge of implementation. It represents everything that we are trying to accomplish in the UCI stem cell program, in that it is innovative and targets an important unmet medical need. We will support this exciting program in all ways we can.”

The Gavin Herbert Eye Institute at UCIwill participate in the trial, which is awaiting UCI institutional review board approval. The University of California has a patent pending on this technology. The startup jCyte has licensed rights to it from the university.

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National Eye Institute awards $3.2M for visionary retina research

Project an effort to better understand how visual data processed before sent to brain.

Human retinal cells taken with adaptive optics scanning laser ophthalmoscopy. Real-time eye tracking allows researchers to optically stimulate individual photoreceptors, as illustrated by the green focused beam in the main figure and in the inset, which shows a magnified mosaic of cones, the cells in the retina responsible for color vision. The dark branched structures are shadows of blood vessels. (Image courtesy of Lawrence Sincich and Kady Bruce, University of Alabama Birmingham.)

By Sarah Yang, UC Berkeley

The National Eye Institute (NEI) has awarded a five-year, $3.2 million grant for a UC Berkeley-led project to map the interaction of retinal cells in an effort to better understand how visual data is processed before it is sent to the brain.

The project is among five awards announced today (May 1) by the NEI as part of its Audacious Goals Initiative, an ambitious program to catalyze research into treatments for blindness. The focus of the initiative is on restoring sight by regenerating neurons and neural connections in the visual system, particularly in the retina.

The NEI is committing up to $17.9 million over five years for this effort.

Austin Roorda, a UC Berkeley professor of optometry and vision science, is the principal investigator of the retinal mapping project. He will be working with E.J. Chichilnisky and Daniel Palanker, both professors of ophthalmology at Stanford University, and B. Hyle Park, an assistant professor of bioengineering at UC Riverside.

The research team will design a system that can not only map cellular interaction in the retina, but can also help monitor the function in regenerated cells. The system will incorporate eye tracking components and adaptive optics.

“We have entered the research phase of the Audacious Goals Initiative. Projects in this first round of AGI funding will bridge gaps in current technology, enabling later phases of the initiative,” said Dr. Paul Sieving, NEI director, in a press statement. Sieving is scheduled to detail the research grants today at the 2015 Association for Research in Vision and Ophthalmology annual meeting.

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Rare mutation causes vitamin A deficiency, eye deformities

Altered protein highlights unique genetic inheritance.

Researchers at the University of Michigan and UC Davis have solved a genetic mystery that has afflicted three unrelated families, and possibly others, for generations. These families have been plagued by a variety of congenital eye malformations, including small eyes with poor vision and the complete absence of eyes. But until now, no one could figure out the genetic basis for these conditions.

By mapping and sequencing family DNA, the research team found mutations in a protein (RBP4) that transports a form of vitamin A called retinol, an essential nutrient for eye development. The mutations create a functional “double-whammy.”

First, the mutated proteins fail to transport retinol to the developing embryo. Then, to make matters worse, they also block the cell surface receptor for RBP4 (called STRA6), keeping healthy proteins from delivering their nutritional payload. The end result is a severe retinol deficiency and subsequent birth defects. The research appears online today (April 23) in the journal Cell.

“Instead of being inactive, the mutated proteins have altered function,” said senior author Tom Glaser, a professor in the Department of Cell Biology and Human Anatomy at UC Davis who began this project at the University of Michigan. “They fail to bind to retinol, but they also plug up the receptor, binding 40 times more tightly than the unmutated protein. The mutants act like goalies, keeping retinol away from the receptors.”

Family  tree ‘invaluable’ to the research

The paper also highlights a unique collaboration between families, clinicians and researchers, according to Christine Nelson, a senior clinical author of the study and professor in the Department of Ophthalmology and Visual Sciences at the University of Michigan’s Kellogg Eye Center. The study arose from Nelson’s discovery that two of her young patients with similar eye malformations were related. The project gained momentum when the team received an unexpected “gift” from the family patriarch — an invaluable family tree that, together with old photographs, revealed a new type of inheritance.

“Some family members only took pictures from one side, or tilted their heads a certain way so they could see better,” Nelson said. “This visual evidence helped us identify eye defects in earlier generations.”

Tracking the path of vitamin A transport and eye defects

RBP4 is secreted by the liver and plays a critical role in eye development. Because retinol is not water-soluble, it needs a vehicle to carry it in the bloodstream to the STRA6 receptor. The transaction becomes even more intricate in utero, as the nutrient must be passed through the placenta from mother to baby.

This complicated transfer process plays a crucial role in how the defect is inherited from one generation to the next. The largest family in the study had endured eye issues for five generations. However, though the mutated gene is dominant, it only causes problems when passed through the mother, often skipping generations. One child inherited the gene through the father and exhibited the trait, but experienced only mild symptoms. The research team had inadvertently discovered a unique form of maternal inheritance.

“When the trait is inherited from the mother, there’s a problem transporting retinol from the mother’s liver to the placenta and from the placenta to the fetus,” said Glaser. “It’s a two-part process and the retinol has to be handed off, like a relay race, to cross between maternal and fetal circulation. When inherited from the father, only one leg of the journey is defective, allowing enough vitamin A to get through to prevent the birth defect.”

This unusual maternal inheritance pattern may have implications for other families experiencing congenital diseases. However, the research is already having profound implications for these particular families. In some cases, mothers and babies have both carried the mutation but experienced no ocular birth defects, showing the defective pathway can be circumvented.

Hope for preventing eye defects in families at risk

“While further clinical research is needed, it appears that we might be able to save a child from blindness with a simple and inexpensive treatment – an extra vitamin A pill,” Nelson said. “This supplementation relies on an alternate pathway, independent of RBP, that delivers another form of vitamin A, called retinyl ester, bypassing the mutations altogether.

Nelson suggests that women with this family history of eye malformations or those who learn that they carry the mutation consult with their obstetricians about taking vitamin A supplements during pregnancy. The discussion should begin before pregnancy since major steps in eye development take place in the first two months of gestation. Thus, a woman might not know she is pregnant when treatment is optimal.

“We’re lucky that nature has created this parallel pathway because vitamin A is so important to a developing fetus,” said Christopher Chou, the study’s first author and a resident physician in emergency medicine at the University of Michigan. “It’s not often you have a genetic defect on which you can directly intervene. This study illustrates how understanding one’s genetic make-up can add a personal touch to medical care.”

Next steps

The researchers still have much work to do. Glaser notes the team would like to map the entire genetic pathway associated with eye malformations. In addition, the study could help researchers investigate other genetic conditions.

“We need to look at genes governing vitamin A transport, as well as transport genes that affect the development of other organs,” Nelson said. “Also, there may be additional diseases that result from defective placental transport.”

Other authors of the research paper, entitled “Biochemical Basis for Dominant Inheritance, Variable Penetrance, and Maternal Effects in RBP4 Congenital Eye Disease,” include: Susan A. Tarlé and Jonathan T. Pribila  (Univ. of Michigan Medical School); Tanya Bardakjian and Adele Schneider (Einstein Medical Center); and Sean Woods (UC Davis). The study was funded by grants from the NIH (EY19497), NIH T32 grants (GM07544 and HD07505), the Midwest Eye Bank and Transplantation Center and the UM Centers for Rare Disease and Genetics in Health and Medicine.

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Unnecessary preoperative testing still done on cataract patients

UCSF researchers find testing based on provider behavior, not patient traits.

By Scott Maier, UC San Francisco

Although routine preoperative testing is not indicated for patients undergoing cataract surgery, researchers at UC San Francisco have found that it is still a common occurrence and is driven primarily by provider practice patterns rather than patient characteristics.

Their study appears in the April 16 issue of the New England Journal of Medicine.

“Our study shows that routine preoperative testing still occurs in Medicare patients undergoing cataract surgery, even though it is one of the safest procedures out there,” said lead author Catherine Chen, M.D., M.P.H., resident physician in the Department of Anesthesia and Perioperative Care at UCSF. “The major professional societies have agreed for more than a decade that routine testing doesn’t improve outcomes from surgery.”

According to the study background, cataract surgery is the most common elective surgery among Medicare beneficiaries, with 1.7 million surgeries annually. The average surgery is just 18 minutes long, and virtually all are performed in an outpatient setting with eye drops for anesthesia.

Chen and her colleagues analyzed a cohort of Medicare beneficiaries undergoing cataract surgery in 2011 to determine the frequency and cost of preoperative testing and office visits in the month before surgery.

Among nearly 441,000 patients studied, 53 percent had at least one preoperative test, and 52 percent had a preoperative office visit in the month before surgery. Testing and office visit expenses were $4.8 million (42 percent) and $12.4 million (78 percent) higher, respectively, than the average monthly expenditures during the preceding 11 months.

However, the researchers found testing varied widely among ophthalmologists and seemed to have little to do with patient characteristics. Although most ophthalmologists did not appear to do additional testing during the preoperative month, a small group of ophthalmologists accounted for more than 84 percent of the excess tests performed.

“The ophthalmologist who operated on the patient was a stronger predictor of whether patients were tested than any other variable we looked at, which implies that it doesn’t matter whether a patient is sick or healthy,” Chen said. “There are certain doctors who will always order tests in their patients just because that patient is having surgery, even though studies have shown that these tests don’t make a difference since cataract surgery itself is so low risk.”

“In this study, we found that the excess testing occurred primarily among a small number of physicians who are readily identifiable using claims data,” said senior author R. Adams Dudley, M.D., M.B.A., director of the Center for Healthcare Value at The Philip R. Lee Institute for Health Policy Studies at UCSF. “This study hopefully will encourage these physicians to examine their practice and make a change, but it also demonstrates that payers like Medicare could use their own data to figure out which doctors they need to talk to about this.”

Chen is careful to point out it is not necessarily the ophthalmologist alone who is driving testing.

“We can’t tell which doctor – the ophthalmologist, the anesthesiologist or the primary care provider – actually ordered the tests,” Chen said. “Ophthalmologists usually work closely with anesthesiologists and primary care physicians to evaluate their patients before surgery. That being said, our study is important because it shows that claims data can be used to eliminate wasteful spending without negatively impacting the quality of care provided to Medicare patients.”

Other UCSF contributors to the New England Journal of Medicine study were Grace Lin, M.D., M.A.S., assistant professor of general internal medicine; Naomi Bardach, M.D., M.A.S., assistant professor of pediatrics; W. John Boscardin, Ph.D., professor of epidemiology and biostatistics; and Adrian Gelb, M.D., Ch.B., professor, Mervyn Maze, M.B., Ch.B., professor, and Michael Gropper, M.D., Ph.D., professor and interim chair, anesthesia and perioperative care. Theodore Clay, M.S., statistician at Clay Software & Statistics, also contributed.

Funding was provided by the Foundation for Anesthesia Education and Research and The Grove Foundation.

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Looking back and ahead, Shiley’s vision remains clear

UC San Diego emerges as regional hub for eye care, research, education, community service.

By Scott LaFee, UC San Diego

Time may blur, but the first quarter-century of the Shiley Eye Center – it celebrates that anniversary this year – remains sharply defined in its accomplishments and focus on the future.

When the $8 million center debuted in 1991, launched by a $1 million leadership gift from the late philanthropist Donald Shiley and his wife, Darlene, it stood alone – quite literally. The neighboring Perlman Ambulatory Care Center (now Perlman Medical Offices) and UC San Diego Thornton Hospital were both two years from completion. More to the point, the new Shiley Eye Center represented the first institution in San Diego entirely dedicated to eye care and science.

“No other major city had been without an eye center,” said Dr. Stuart Brown, then-chair of the Department of Ophthalmology and the center’s founding director at the opening gala in 1991. “And now we will be allowed to achieve our mission and our greatest potential.”

The ambition of the Shiley team was to establish an eye center unrivaled in the region. To a remarkable degree, they have succeeded. It’s a vision that has accelerated under the current Shiley director and ophthalmology chair, Dr. Robert N. Weinreb. “The Shiley has emerged as a hub for clinical care excellence, outstanding vision research and broad-based eye health education. By investing in unsurpassed facilities, equipment and brainpower, we have become a destination for preventing and curing blinding eye diseases for the residents of San Diego and beyond.” said Weinreb.

This week, Shiley expands upon that success, changing its name to the UC San Diego Donald P. and Darlene V. Shiley Eye Institute, which will encompass the Shiley Eye Center, the Anne F. and Abraham Ratner Children’s Eye Center, the Hamilton Glaucoma Center and the Joan and Irwin Jacobs Retina Center. The institute is part of the UC San Diego Health System.

“The new name more accurately captures the fullness of the work being done at Shiley,” said UC San Diego Chancellor Pradeep K. Khosla. “The institute and department of ophthalmology, working hand-in-hand with the School of Medicine and other programs across campus, will leverage every possible tool and expertise, from genetics, bioengineering and pharmacy to pathology, neurosciences and stem cell research, to improve the treatment of eye diseases, find new cures and hasten the day when blindness is entirely preventable.”

The institute will include the new Richard C. Atkinson Laboratory for Regenerative Ophthalmology, created last year with an anonymous $6.5 million gift from a grateful patient. The new lab will investigate cell replacement therapies, tissue engineering and other biomedical advances to reverse vision loss and blindness. Researchers will explore novel stem cell approaches and work closely with the Sanford Clinical Stem Cell Center at UC San Diego Health System, which was established in 2013.

Nearby, a new Vision Research Center is in the early stages of planning along with the creation of a framework to fund the project. The center is envisioned to accelerate the translation of new research into treatments for patient with blinding ophthalmic diseases.

“The center is intended to help bridge the gap between laboratory and clinic by bringing together brilliant minds and diverse talents in a shared facility,” said Weinreb. “This integrated approach will speed the transformation of discoveries into clinical applications that can be tested through clinical trials.”

If past is prologue, the future looks bright. Over the years, Shiley physicians and researchers have made major contributions to preventing and curing eye diseases such as macular degeneration, glaucoma, diabetic retinopathy, corneal disorders and cataracts.

Recently, for example, they have been involved in developing an artificial retina, a smart contact lens that wirelessly monitors intraocular pressure (a key risk factor in glaucoma) and the use of self-renewing stem cells to repair or restore vision lost to diseases like macular degeneration, glaucoma and corneal opacity. They are even helping explore the possibility of whole eye transplants.

Clinical care remains a cornerstone. In 2014, there were 106,470 patient visits and 4,862 surgeries. Patients ranged in age from one day to 105 years. The Shiley Eye Mobile conducted 12,238 vision screenings, 2,011 eye exams, dispensed 1,288 pairs of free glasses and referred 107 children for more serious follow-up care.

“It was always very clear that my late husband had a special place in his heart for the Shiley Eye Center,” said Darlene Shiley. “I will never forget how moved he was by Dr. Brown’s description of the work being done and the work that still needed to be addressed. And now, decades later, Dr. Weinreb is focused on patient-centric care excellence and leading the Shiley into new areas of eye research and treatment. Successful past, bright future – how lucky we all are to have such dedicated physicians, researchers, staff and eager volunteers.”

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Early retina cell changes in glaucoma ID’d

Specific structural features, cell types in retina may be key factors in glaucoma progression.

Example of retinal ganglion cells with dendrites in the retina of a healthy eye.

By Heather Buschman, UC San Diego

Glaucoma, the second leading cause of blindness, usually stems from elevated eye pressure, which in turn damages and destroys specialized neurons in the eye known as retinal ganglion cells. To better understand these cellular changes and how they influence the progression and severity of glaucoma, researchers at the UC San Diego School of Medicine and Shiley Eye Institute turned to a mouse model of the disease. Their study, published Feb. 10 in The Journal of Neuroscience, reveals how some types of retinal ganglion cells alter their structures within seven days of elevated eye pressure, while others do not.

“Understanding the timing and pattern of cellular changes leading to retinal ganglion cell death in glaucoma should facilitate the development of tools to detect and slow or stop those cellular changes, and ultimately preserve vision,” said Andrew D. Huberman, Ph.D., assistant professor of neurosciences, neurobiology and ophthalmology. Huberman co-authored the study with Rana N. El-Danaf, Ph.D., a postdoctoral researcher in his lab.

Retinal ganglion cells are specialized neurons that send visual information from the eye’s retina to the brain. Increased pressure within the eye can contribute to retinal ganglion cell damage, leading to glaucoma. Even with pressure-lowering drugs, these cells eventually die, leading to vision loss.

In this study, Huberman and El-Danaf used a mouse model engineered to express a green fluorescent protein in specific retinal ganglion cells subtypes. This tool allowed them to examine four subtypes of retinal ganglion cells. The different cell types differ by the location in the eye to which they send the majority of their dendrites (cellular branches). Within seven days of elevated eye pressure, all retinal ganglion cells that send most or all of their dendrites to a region of the eye known as the OFF sublamina underwent significant rearrangements, such as reductions in number and length of dendritic branches. Retinal ganglion cells with connections in the ON part of the retina did not.

“We are very excited about this discovery,” Huberman said. “One of the major challenges to the detection and treatment of glaucoma is that you have to lose a lot of cells or eye pressure has to go way up before you know you have the disease. These results tell us we should design visual field tests that specifically probe the function of certain retinal cells. In collaboration with the other researcher members of the Glaucoma Research Foundation Catalyst for a Cure, we are doing just that and we are confident these results will positively impact human patients in the near-future.”

This research was funded, in part, by the Glaucoma Research Foundation Catalyst for a Cure and the E. Matilda Ziegler Foundation for the Blind.

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Newly named Shiley Eye Institute projects bigger, bolder vision

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Newly named Shiley Eye Institute projects bigger, bolder vision

UC San Diego emerges as regional hub for eye care, research, education, community service.

By Scott LaFee, UC San Diego

Reflecting its emergence as a regional hub for unparalleled clinical care, research, education and community service, the UC San Diego Shiley Eye Center has been renamed the UC San Diego Donald P. and Darlene V. Shiley Eye Institute, encompassing the Shiley Eye Center, the Anne F. and Abraham Ratner Children’s Eye Center, the Hamilton Glaucoma Center and the Joan and Irwin Jacobs Retina Center.

“The new name more accurately captures the fullness of the work being done at Shiley,” said Pradeep Khosla, chancellor of the University of California, San Diego. “The institute and Department of Ophthalmology, working hand-in-hand with the School of Medicine and other programs across campus, will leverage every possible tool and expertise, from genetics, bioengineering and pharmacy to pathology, neurosciences and stem cell research, to improve the treatment of eye diseases, find new cures and hasten the day when blindness is entirely preventable.”

Robert N. Weinreb, M.D., chair and Distinguished Professor of Ophthalmology and director of the Shiley Eye Institute, said the institute’s emphasis would remain focused upon achieving excellence – in the clinic and in the laboratory. “The department will continue to partner with groups in San Diego and throughout the world to translate research into better vision. We also will continue to nurture and grow our programs for community outreach and continuing medical education for physicians.”

The Shiley Eye Institute, part of UC San Diego Health System, employs 227 faculty and staff. In 2014, there were 106,470 patient visits and 4,862 surgeries. The Shiley Eye Mobile conducted 12,238 vision screenings, 2,011 eye exams, dispensed 1,288 pairs of free glasses and referred numerous children for more serious follow up care.

“It was always very clear that my late husband had a special place in his heart for the Shiley Eye Center,” said Darlene Shiley, a staunch supporter of the center since it was founded in 1991. “I will never forget how moved he was by (former director and department chair) Dr. Stuart Brown’s description of the work being done and the work that still needed to be addressed.  And now, decades later, Dr. Robert Weinreb is focused on patient-centric care excellence and leading the Shiley into new areas of eye research and treatment.  Successful past, bright future – how lucky we all are to have such dedicated physicians, researchers, staff and eager volunteers.”

Doctors and researchers at Shiley have made measurable progress in addressing some of the primary diseases of vision, such as macular degeneration, glaucoma, diabetic retinopathy, corneal and retinal disorders and cataracts. Patients range in age from 1 day to 105 years old.

Shiley physician-scientists are actively involved in diverse research and scholarship, from defining all of the cell types and synaptic connections that link the eyes to the brain, part of President Obama’s BRAIN Initiative, developing biosensors and an artificial retina, even exploring the possibilities of whole eye transplants. In 2013, Shiley Eye Center was ranked fourth in the nation in funding to departments of ophthalmology from the National Institutes of Health. Last year, the Department of Ophthalmology was awarded a prestigious K12 grant from the NIH to train clinician scientists, one of just a few such grants in the country. In 2014, Shiley researchers published 205 peer-reviewed studies and conducted 29 clinical trials.

The institute will include the new Richard C. Atkinson Laboratory for Regenerative Ophthalmology, created last year with an anonymous $6.5 million gift from a grateful patient. The new lab will investigate cell replacement therapies, tissue engineering and other biomedical advances to reverse vision loss and blindness. Researchers will explore novel stem cell approaches and work closely with the Sanford Clinical Stem Cell Center at UC San Diego Health System, which was established in 2013.

A new Vision Research Center is in the early stages of planning along with the creation of a framework to fund the project. The center is envisioned to accelerate the translation of new research into treatments for patient with blinding ophthalmic diseases.

“The center is intended to help bridge the gap between laboratory and clinic by bringing together brilliant minds and diverse talents in a shared facility,” said Weinreb. “This integrated approach will speed the transformation of discoveries into clinical applications that can be tested through clinical trials.”

The new Shiley Eye Institute embraces the larger mission of UC San Diego, its schools and programs and the UC San Diego Health System, said David Brenner, M.D., vice chancellor of health sciences and dean of the School of Medicine. “Our goal is unprecedented collaboration across all disciplines, moving basic science to real-world applications as quickly and as effectively as possible and doing so in a way that truly improves patient care and lives. I think people will see that vision come to life in the institute.”

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Stein, Doheny eye institutes join forces

Affiliation expands UCLA faculty, adds new clinics to UCLA Health, improves patient access.

Doris and Jules Stein (Photo from Stein Eye Institute archives)

By Elaine Schmidt, UCLA

Two of the nation’s top eye institutes have united in an affiliation that will improve patients’ access to leading vision specialists.

UCLA’s Stein Eye Institute and the Doheny Eye Institute — both created by families whose legacies helped shape Los Angeles — have joined forces to offer the best in patient care, vision research and training for future eye specialists. The affiliation adds 14 clinicians and researchers from Doheny, formerly associated with the University of Southern California, to the ophthalmology faculty at the David Geffen School of Medicine at UCLA.

“The Stein–Doheny affiliation is a beautiful fit,” said Dr. Bartly Mondino, director of the Stein Eye Institute and chair of ophthalmology at the David Geffen School of Medicine at UCLA. “We share similar missions and have a long history of collaboration. This partnership expands UCLA’s footprint tremendously by providing patients with greater access to the top doctors in cornea, retina, glaucoma, neuroophthalmology and oculoplastics.”

As part of the agreement, Doheny’s clinics will join the UCLA Health network. Two Doheny Eye Center UCLA sites will expand community access to specialty care in newly renovated offices in Arcadia and Fountain Valley. A third clinic, in a new medical–surgical suite in Pasadena, will act as Doheny Eye Center UCLA’s primary hub.

Each organization will preserve its identity while combining clinical and teaching operations. Both institutes have earned international recognition for the quality of their patient care and research. U.S. News and World Report’s 2015 “Best Hospitals” survey ranked the combined Stein Eye and Doheny Eye institutes as the No. 5 center for ophthalmology based on feedback from specialists in the field.

“Since our establishment in 1947, the Doheny Eye Institute has worked to become the premier vision research and education eye institute in the world through the discovery of new knowledge, innovative eye-care therapies and the education of the leaders of ophthalmology and vision science,” said Ed Landry, chair of the Doheny Eye Institute board of directors. “UCLA and the Stein Eye Institute share our values and high standards for education, patient care and research. We expect that the combination of our two leading programs will result in even greater recognition and accomplishments.”

“We are honored to work with the Doheny Eye Institute to improve patient care throughout Southern California, while simultaneously extending the Stein Eye Institute’s research and educational outreach, which hold immense value for the nation and world,” said Dr. David Feinberg, president of the UCLA Health System, CEO of the UCLA Hospital System and associate vice chancellor of the Geffen School of Medicine. “We appreciate this rare and unique opportunity to strengthen relationships with our distinguished colleagues at Doheny, many of whom have long collaborated with us in serving the Los Angeles community.”

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New therapy holds promise for restoring vision

It has several advantages over other sight restoration therapies now under investigation.

Benjamin Gaub and John Flannery observing a mouse in a water maze, in which the mouse swims to a platform designated by bright flashing lights. (Photo by Mervi Kuronen)

By Robert Sanders, UC Berkeley

A new genetic therapy not only helped blind mice regain enough light sensitivity to distinguish flashing from non-flashing lights, but also restored light response to the retinas of dogs, setting the stage for future clinical trials of the therapy in humans.

The therapy employs a virus to insert a gene for a common ion channel into normally blind cells of the retina that survive after the light-responsive rod and cone photoreceptor cells die as a result of diseases such as retinitis pigmentosa. Photoswitches – chemicals that change shape when hit with light – are then attached to the ion channels to make them open in response to light, activating the retinal cells and restoring light sensitivity.

Afflicting people of all ages, retinitis pigmentosa causes a gradual loss of vision, akin to losing pixels in a digital camera. Sight is lost from the periphery to the center, usually leaving people with the inability to navigate their surroundings. Some 100,000 Americans suffer from this group of inherited retinal diseases.

In a paper appearing online this week in the early edition of the journal Proceedings of the National Academy of Sciences, University of California, Berkeley, scientists who invented the photoswitch therapy and vision researchers at the School of Veterinary Medicine of the University of Pennsylvania (PennVet) report that blind mice regained the ability to navigate a water maze as well as normal mice.

The treatment worked equally well to restore light responses to the degenerated retinas of mice and dogs, indicating that it may be feasible to restore some light sensitivity in blind humans.

“The dog has a retina very similar to ours, much more so than mice, so when you want to bring a visual therapy to the clinic, you want to first show that it works in a large animal model of the disease,” said lead researcher Ehud Isacoff, professor of molecular and cell biology at UC Berkeley. “We’ve now showed that we can deliver the photoswitch and restore light response to the blind retina in the dog as well as in the mouse, and that the treatment has the same sensitivity and speed of response. We can reanimate the dog retina.”

The therapy has several advantages over other sight restoration therapies now under investigation, says vision scientist John Flannery, UC Berkeley professor of vision science and of molecular and cell biology. It uses a virus already approved by the Food and Drug Administration for other genetic therapies in the eye; it delivers an ion channel gene similar to one normally found in humans, unlike others that employ genes from other species; and it can easily be reversed or adjusted by supplying new chemical photoswitches. Dogs with the retinal degeneration provide a key test of the new therapy.

“Our ability to test vision is very, very limited in mice because, even in the healthy state, they are not very visual animals, their behaviors are largely driven by their other senses,” he says. “Dogs have a very sophisticated visual system, and are being used already for testing ophthalmic gene therapy.”

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Edie & Lew Wasserman Building opens at UCLA

Research, patient care facility completes trio of buildings envisioned for Stein Eye Institute.

Casey Wasserman, the grandson of UCLA philanthropists Edie and Lew Wasserman, welcomes guests at the official opening of the new landmark research and patient-care building named for his grandparents, whose generosity made it possible. (Photo by Reed Hutchinson, UCLA)

Campus officials dedicated the Edie & Lew Wasserman Building, a new landmark research and patient care facility at UCLA, at a festive ceremony Tuesday. Named to honor the late philanthropists Edie and Lew Wasserman, whose generosity made the striking structure possible, the state-of-the-art facility will meet the expanding needs of the Stein Eye Institute and provide space for UCLA’s Department of Neurosurgery and Institute of Urologic Oncology.

“This world-class complex culminates years of planning to ensure the effective use of several exceptionally generous gifts to benefit the public,” Chancellor Gene Block said, noting the facility’s diverse uses for patient care, medical research and physician training across multiple fields. “It is an enduring legacy of Edie and Lew Wasserman, who were among UCLA’s most ardent enthusiasts. They gave selflessly not only to enhance vision care, but also to establish undergraduate student scholarships in the UCLA College and graduate student fellowships in film production, among other gifts.”

Designed by Richard Meier and Partners Architects, the $115.6 million project is a LEED gold-certified “green,” six-story building encompassing100,000 square feet. A stunning example of modern architecture dominated by clean lines, white terracotta and pale oak, the facility features floor-to-ceiling windows that flood the spacious rooms with natural light and reveal dramatic views of campus.

A three-story glass wall surrounds the main lobby, where a sculpture of two oversized pairs of glasses commands the spotlight. Inspired by the Wassermans’ signature eyewear, the spectacles pay homage to the couple’s infinite vision and long-standing commitment to preventing blindness and restoring eyesight.

Casey Wasserman, the grandson of Edie and Lew Wasserman, recalled that he was a UCLA senior when he attended his first architectural meeting about the Wasserman building with his grandfather in 1996. Eighteen years later, he found himself participating in the ceremonial ribbon-cutting with his wife and children at Tuesday’s event.

“The motto of UCLA is ‘Let There Be Light,’” said Wasserman, president and chief executive officer of the Wasserman Foundation. “The first thing that (lead architect) Michael Palladino said to us was, ‘These buildings are so dark, and you’re treating people who have eye challenges.  We need the greatest light in the world and live in the city that provides us with that opportunity.’  There certainly is light here. I’m enormously pleased and proud to see my grandparents’ dream come to fruition in close collaboration with UCLA.”

The initial vision for the institute has its roots in the 1960s, when Hollywood agent and studio chief Lew Wasserman, Music Corporation of America founder Jules Stein and then-UCLA Chancellor Franklin Murphy imagined a trio of facilities dedicated to restoring and preserving eyesight. The first building, the Jules Stein Eye Institute, opened its doors in 1966, and, in 1989, Stein Plaza expanded with the creation of the Doris Stein Eye Research Center, named after Jules Stein’s wife.

“We’re here to celebrate the future,” said Dr. A. Eugene Washington, vice chancellor of UCLA Health Sciences and dean of the David Geffen School of Medicine at UCLA,  in his remarks at the podium. “The Edie & Lew Wasserman Building is a beautiful symbol of UCLA’s collaborative spirit and our global impact. When you first look at it, what jumps out at you is that it is a de facto work of art.”

The Wasserman building’s three lower floors are dedicated to the Stein Eye Institute. The new center features six lower-level operating rooms, with orbital and ophthalmic plastic surgery on the first floor, and cataract and refractive surgery on the second floor. Each practice area includes procedure space and clinics, enabling physicians to perform patient exams, testing and surgery in the same location.

“The welcome addition of the magnificent Edie & Lew Wasserman Building to Stein Plaza will greatly enhance the Stein Eye Institute’s continued evolution into the leading eye care, vision research and educational center of the 21st century,” said Dr. Bartly J. Mondino, director of the Stein Eye Institute and the Bradley R. Straatsma, MD, Chair in Ophthalmology at the David Geffen School of Medicine at UCLA. “With the opening of the Wasserman building and our recent affiliation with the Doheny Eye Institute, this has truly been a banner year for the Stein Eye Institute.”

By moving its surgical center to the Wasserman building, the Stein Eye Institute will be able to expand the lab space in the Jules Stein Building to accommodate cutting-edge research, like gene and stem cell therapy for treating eye disease, added Mondino.

The UCLA Institute of Urologic Oncology (IUO) on the third floor is led by a multidisciplinary team of scientists and physicians dedicated to expediting the development of new therapies for the treatment of kidney, bladder, testicular and prostate cancers.

Patients benefit from the IUO’s collaborative approach, top diagnostic tools, expertise in robotic surgery and the combined experience of UCLA experts, who often treat the most complicated urologic cancer cases. A board representing all genitourinary specialties meets at the IUO to discuss complicated and challenging tumor cases referred to UCLA.

“This is a new concept; very few centers in the country, if any, are practicing such truly unified medicine,” said Dr. Arie Belldegrun, IUO director. “Patients are able to see and obtain opinions from all experts dealing with their disease in one sitting, rather than scheduling separate appointments with each specialist. It’s very convenient and patient-friendly.”

The Wasserman building’s innovative philosophy is also reflected on the top two floors housing the UCLA Global Neurosurgery Center. The new facility unites the entire Department of Neurosurgery faculty, which was previously scattered across eight buildings. The center also features a telemedicine command center that allows surgeons to continuously monitor patients in Ronald Reagan UCLA Medical Center; UCLA Medical Center, Santa Monica; and community hospitals across California.

A new clinic boasts six exam rooms, two consultation suites and spaces for multidisciplinary teams of physicians to collaborate. A teleconferencing suite features a multimedia board room and a 70-seat IMAX-style conference center that will allow experts worldwide to pool their knowledge and accelerate surgical solutions for patients.

A simulation center will enable surgeons and trainees to download images of patients’ brain anatomy to rehearse complex cases before entering the operating room. The virtual-reality environment will allow surgeons to select instruments, choose the best entry points and identify complicating factors in order to reduce medical risks and ensure successful results.

“We’re reinventing the future of neurosurgery with this facility,” said Dr. Neil Martin, chair of neurosurgery at UCLA. “This new center provides us with a platform to truly revolutionize how we work together as a team, how we train the neurosurgeons of the future, and how we ensure that our patients have the very best outcomes.”

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