The Kellogg Eye Center has one of the world’s largest clinical and research teams devoted to retinal dystrophies—blinding eye disorders caused by genetic errors in rods and cones and their support structures. Until recently, doctors could do no more than make a tentative diagnosis and suggest visual aids.
Now that many culprit genes have been identified, things are about to change. Diagnoses have become more definitive, and promising gene-replacement treatments are on the way, including the first FDA-approved gene therapy for RPE65 defects. This exciting development opens the door for what will hopefully be many more products to help patients with other eye diseases in the future.
To get there, clinical trials of safety and effectiveness need to continue. Some may come from the work of our Kellogg team members:
John Heckenlively, M.D., is the senior member of our retinal dystrophies team. The Paul R. Lichter Professor of Human Genetics, Heckenlively came to Kellogg from a professorship at the University of California-Los Angeles. A medical graduate of the University of Colorado, he completed an ophthalmology residency at the University of Kentucky, a vitreoretinal fellowship at UCLA and a retinal dystrophy fellowship at Johns Hopkins University.
Dr. Heckenlively is an eminent research scientist in the field of retinal dystrophies and autoimmune retinopathy. He has identified more than 110 different genetic mouse-eye models for human retinal diseases. For many of those diseases, he later found the same defective gene in humans.
Thiran Jayasundera, M.D., a native of Sri Lanka, immigrated to New Zealand at age 13. Completing medical studies at the University of Auckland in 2000, he briefly considered neurosurgery, but an exciting rotation in Australia persuaded him to study ophthalmology. He decided to devote his career to retinal dystrophies. He later took a fellowship at Kellogg under the mentorship of John Heckenlively, followed by a two-year medical and surgical retinal fellowship at McGill University in Montreal. He joined the Kellogg faculty in 2011.
At Kellogg, “Dr. J” uses a National Institutes of Health K23 grant to study patient-reported outcomes as a measure of treatment efficacy. He directs the Argus II program, in which 10 patients blind from retinal dystrophy have undergone surgery for a visual prosthesis that provides them with rudimentary vision. He has edited a forthcoming atlas that provides clinical exam and photographic data about diseases caused by 80 different abnormal genes associated with retinal dystrophies. Dr. Jayasundera is a co-investigator in the natural history studies and gene therapy trials that are underway at Kellogg.
Abigail Fahim, M.D., Ph.D., received an M.D. and a Ph.D. in genetics from U-M. She completed a postdoctoral year in retinal genetics at the University of Texas-Houston. Returning to Ann Arbor, she completed an ophthalmology residency and undertook fellowships in retinal dystrophy and in medical retinal diseases at Kellogg. Appointed to the Kellogg faculty in 2017, Dr. Fahim is preparing in vitro stem cells induced to become retinal pigment epithelial cells containing the abnormal genetic imprint of choroideremia, a vision-threatening disorder. Her research seeks to discover and block the abnormal products of this cell line to prevent blindness.
David Zacks, M.D., Ph.D., joined the team in 2002. He holds an M.D. and Ph.D. from the Albert Einstein College of Medicine, Yeshiva University. He finished his ophthalmology residency in 2000 and his vitreoretinal fellowship in 2002, both at the Massachusetts Eye and Ear Infirmary, Harvard University.
At Kellogg, he implanted the Argus II device. Dr. Zacks’ research centers on retinal cell death following retinal detachment.
Cagri Besirli, M.D., Ph.D., specializes in retinal illnesses of children. He emigrated from Turkey at age 17 to enter U-M as an undergraduate. He went on to obtain an M.D. and Ph.D. from Washington University in St. Louis, and returned to Michigan for his residency in ophthalmology and fellowship in retinal diseases. He also had additional pediatric retinal training with Mike Trese, M.D., and colleagues at Associated Retinal Consultants.
Dr. Besirli's research focuses on using imaging tools to study retinal blood vessels and factors that lead to apoptosis, a programmed cell death that is common in many body tissues. His laboratory has developed an inhibitor that he hopes will protect the retina from blinding childhood disorders.
Debra Thompson, Ph.D., is a professor of ophthalmology and visual sciences and professor of biological chemistry at U-M. Her laboratory has helped to identify gene mutations in retinal dystrophies that disrupt the conversion of light energy into signals that the brain can interpret as vision. Professor Thompson and her colleagues are using this information to develop treatments that can be submitted to clinical trials, including gene therapy approaches in collaboration with Robin Ali, Ph.D.
Naheed Khan, Ph.D., is the team’s electrophysiologist. Born in Hyderabad, India, she holds a Ph.D. in biomedical engineering from Ohio State University. At scientific meetings, she encountered Paul Sieving, M.D., Ph.D., then a professor at Kellogg (and now director of the National Eye Institute), who was so impressed with her work that he offered her a position at Kellogg. She became involved with diagnostic electrophysiological and psychophysical studies for Kellogg physicians, and has traveled to Pondicherry, India, to monitor Aravind Eye Hospital’s new retinal dystrophy service. She is designing the retinal testing protocols for the upcoming natural history and gene therapy trials.
Kari Branham, M.S., is one of the team’s two genetic counselors. She holds a master’s degree in genetic counseling from U-M. Intrigued by medical genetics, she studied genetic damage in individuals who cleaned up the Chernobyl nuclear reactor accident at Lawrence Livermore National Laboratory. As a genetics counselor at Kellogg, she has witnessed the discovery of 281 genes related to retinal dystrophies. “Those discoveries have completely changed our role as counselors,” she said. "Although we have more genetic information now, we do not always know if it is relevant to the patient’s condition. Part of my job is to interpret this information.”
Dana Schlegel, M.S., M.P.H., who joined the team in 2014, is its second genetic counselor. Following graduation from Harvard University, she joined the Peace Corps, where she served as a high school biology teacher in Mozambique. Fluent in Portuguese, she was an interpreter at Boston’s Dana-Farber Cancer Institute before she came to U-M for a dual master’s degree in genetic counseling and public health (health behavior and health education). She has a passion for genetics education and, in addition to her clinical work with dystrophy patients, has been designing the genetics training curriculum for Kellogg’s retinal dystrophy fellowship program.
Robin Ali, Ph.D., is a visiting professor of ophthalmology and a leader in the field of retinal gene therapy. His primary academic position is at University College London, where he pioneered an efficient way to deliver replacement genes to the retina by incorporating them into viruses. His laboratory showed that gene therapy works in several mouse models of retinal dystrophy and can be performed safely in humans. He has established a pipeline of therapies that are being tested in clinical trials.
Kellogg will participate in several of these trials, testing treatments for Leber congenital amaurosis, a blinding disease of young children; achromatopsia, a childhood disorder of retinal cone photoreceptors; and X-linked retinitis pigmentosa. Professor Ali is also developing photoreceptor cell transplantation as a strategy for treating patients who have lost such cells due to retinal disease. Having shown that transplanted stem cell-derived photoreceptors can improve vision in mice, his laboratory continues to work toward developing a cellular therapy that can be tested in clinical trials. At Kellogg, he collaborates with Rajesh Rao, M.D., to establish clinical trials of stem cell-derived photoreceptor transplantation.
Adrienne Chen, Ph.D., is a research specialist at Kellogg working under the direction of Professor Robin Ali. A native of Taiwan, she holds a Ph.D. in virology from Harvard University and did postdoctoral work at Northwestern University. In 2014, she came to Kellogg to work with Professor Ali on establishing natural history studies and gene therapy trials for retinal dystrophies. “Our whole team is really excited about initiating these trials,” she said. A special challenge is developing a maze test that will be used to judge how well patients can navigate after receiving gene therapy. The maze is located at the U-M Transportation Research Institute in space generously shared by U-M professor Michael Flannagan, Ph.D.
The retinal dystrophy team also has two visiting scholars: Fernanda Abalem de Sa Carricondo, M.D., and Badr Alahmadi, M.D.
Dr. Abalem, a native of Brazil, completed her medical and ophthalmology studies in Rio de Janeiro. After obtaining a master’s degree in ocular inflammation, she moved to the University of São Paulo for a four-year fellowship in retinal diseases. Realizing that the care of retinal dystrophies was an unmet need in Brazil, she decided to dedicate her career to that field. She will found a retinal dystrophies program at University of São Paulo and link it to the work at Kellogg.
Dr. Alahmadi, who is from Saudi Arabia, has been working on measures of contrast sensitivity in patients with retinal dystrophies.
The team is dedicated to accelerating progress for treating and curing inherited retinal diseases.