Impact of Rho Kinase Inhibition on Morphology and Function of Rod and Cone Synapses after Retinal Detachment

ABSTRACT

Retinal detachment (RD) is a form of retinal injury. Using a large animal model of RD, we have shown that RD induces a change in retinal biochemistry (e.g., increased activated RhoA) within the area of detachment as well as outside the area of the RD. This change is accompanied by changes in retinal anatomy, i.e., separation of the photoreceptor presynaptic terminals from the bipolar cell postsynaptic terminals (termed synaptic disjunction in rod photoreceptors and synaptic disruption in cone photoreceptors). Rho kinase inhibitors reduce these RD-induced anatomic changes, which persist in controls even after retinal reattachment, and improve psychophysical measures of retinal recovery (e.g., scotopic and photopic electroretinogram responses) after retinal reattachment beyond the improvement observed with reattachment alone. We posit that the visual outcome after RD (spontaneous or iatrogenic) might be improved with Rho kinase inhibitors. These results have implications for subretinal gene therapy as well as the development of models of traumatic brain injury.

BIOGRAPHY

Dr. Marco Attilio Eugenio Zarbin, M.D., Ph.D., F.A.C.S. received a B.A. (biochemistry) from Dartmouth College (Phi Beta Kappa, summa cum laude) in 1978. Dr. Zarbin was awarded degrees in medicine (M.D.) and pharmacology (Ph.D.), in 1984. He graduated from the Hopkins Medical School as a member of the Alpha Omega Alpha honor society and completed an ophthalmology residency at the Wilmer Ophthalmological Institute (Johns Hopkins Hospital) 1985-1988. Dr. Zarbin completed fellowships in vitreoretinal surgery and in medical retinal disease at the Wilmer Ophthalmological Institute as a Heed Ophthalmic Foundation Fellow and was an Assistant Chief of Service at Wilmer in 1989. From 1990-1993, an Assistant Professor of Ophthalmology at the University of California, San Francisco, and as Chief of the Division of Ophthalmology at the Department of Veterans Affairs Medical Center, San Francisco. Appointed Chair of the Institute of Ophthalmology and Visual Science, New Jersey Medical School, Rutgers, and Chief of Ophthalmology at University Hospital, Newark, N.J. in January 1994. He is the Alfonse A. Cinotti, MD/Lions Eye Research Professor of Ophthalmology and Neuroscience at Rutgers New Jersey Medical School (RNJMS).

Dr. Zarbin’s research is focused on developing treatments for age-related macular degeneration, the leading cause of blindness in persons over age 55 in the United States. Dr. Zarbin also collaborates with Prof. Ellen Townes-Anderson in the development of sight-preserving therapy for patients with retinal detachment. This research has been supported by the Department of Defense as well as Aerie Pharmaceuticals. Dr. Zarbin has co-authored 248 peer-reviewed scientific publications, 123 book chapters, 31 reviews and editorials, and 38 reports. He has co-edited one book on age-related macular degeneration, two books on cell-based therapy for retinal degenerative disease, and two books on the management of diabetic retinopathy.

Currently, Dr. Zarbin serves as an Editor of Ophthalmology and Ophthalmology Retina and also as a member of the Board of Trustees of the Society of Heed Fellows. Dr. Zarbin is a past President of the Association of University Professors of Ophthalmology as well as of the American Ophthalmological Society. Dr. Zarbin has received a LifeAchievement Award from the American Academy of Ophthalmology, a Leadership Award from the Polish Academy of Ophthalmology, and a Distinguished Service Award from the Association for Research in Vision and Ophthalmology. Dr.Zarbin's clinical practice is limited to medical and surgical diseases of the retina and vitreous.