Research & Publications
Age-related Macular Degeneration
Stem Cell Therapy for Retinal Degenerations
Artificial Retinal Prostheses
Extensive Research Description
I have a long-standing interest in the cell biology of retinal degenerations, as well as the use of cell based therapy for the treatment of retinal degenerations, including retinitis pigmentosa, Stargardt’s disease, and atrophic age-related macular degeneration (AMD). The early part of my career was devoted to understanding the role of the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris, and how retinal RPE-dependent changes in postoperative choriocapillaris perfusion limited visual recovery after submacular membrane removal. We made the important observation that absence or dysfunction of the native RPE leads to choriocapillaris atrophy in animal models. This was important, as we and others had noted that choriocapillaris atrophy develops after the removal of choroidal neovascularization in type 1 neovascularization (beneath the RPE, predominant in AMD) more frequently than type 2 choroidal neovascularization (internal to the RPE, in histoplasmosis and other diseases).
Due to this finding, efforts were directed at replacing the RPE in wet and atrophic macular degeneration. We demonstrated that atrophy of the choriocapillaris developed in patients after subretinal membrane removal in wet AMD and other disorders, and that this limited visual recovery after surgery. Simultaneously we demonstrated that native RPE was removed with the choroidal neovascular membrane in patients with exudative AMD; in animal models, removal of healthy RPE leads to atrophy of the subjacent choriocapillaris.
Our lab performed some of the important early studies to evaluate the effects of Bruch’s membrane disease on the initial attachment, survival and proliferation of transplants placed in the subretinal space. We made the important observation that the survival and proliferation of RPE transplants was limited by the status of the host Bruch’s membrane, and showed that Bruch’s membrane can be reengineered to ensure graft survival.
I was involved in early studies on RPE and photoreceptor transplants in humans and have been part of the recent publication of a phase 1 / 2 clinical trial showing the safety and possible efficacy of embryonic stem cell-derived RPE transplants for atrophic AMD and Stargardts disease. Our efforts in this area are continuing. In addition, we have focused on recent work on attempting to prevent some of the early damage that occurs in age-related macular degeneration, by identifying some of the early oxidative stress pathways in this disease, as well as identifying molecular targets for preventing disease progression.
Over the last few years, we have developed a new research interest on using statistical techniques to determine the natural history of retinal degenerations. This has been a fruitful area of investigation, that has led to a better understanding disease progression in a wide range of disorders that include geographic atrophy in age-related macular degeneration, central atrophy in Stargardts disease, and disease progression in choroideremia. Our long term goal is to use meta analysis techniques to improve our understanding of drug efficacy in clinical trails for these disorders.