Age-related Macular Degeneration (AMD) is the leading cause of blindness in persons over age 55 in the United States and Western Europe. In 80- 90% of cases, severe visual loss is caused by the growth of choroidal neovascular membranes (CNVs) under the RPE and retina. While laser therapy is the only proven treatment for CNVs a minority of patients are candidates for treatment, which is complicated by relatively poor visual outcome and a high rate of recurrent disease. Our desire to carry our RPE debridement, RPE transplantation, and growth factor treatment studies arises from the development of a new surgical technique (subretinal dissection and excision of CNVs) to treat the exudative complications of AMD. Excised CNVs are associated with overlying RPE and Bruch's membrane fragments. Thus, a large area of RPE is debrided as a consequence of CNV removal. We believe removal of RPE limits photoreceptor (and visual) recovery. We will model CNV-associated RPE removal by mechanically debriding RPE from Bruch's membrane. We will determine whether RPE transplantation and/or growth factor therapy reverses these changes. These experiments may establish a basis for RPE transplantation in humans following surgical removal of CNVs. The effect of varying the surface area of debridement on photoreceptor survival centrally will be described. The time course of retinal degeneration following debridement will be described. The ability of proliferating RPE to migrate from the edge into the center of the debrided area and to rescue overlying and/or adjacent photoreceptors will be assessed. For growth factor studies, the ability of basic fibroblast growth factor to prevent retinal degeneration induced by RPE debridement will be assessed. For RPE transplantation, a suspension of cultured cells is then transplanted over the tapetum. Transplanted RPE are identified by their pigmentation, and, in some cases, by fluorescent labels or by a marker gene (pSV GAL). We will evaluate different vehicles for RPE delivery, determine the number of RPE cells needed to repopulate a debrided surface, and evaluate homologous (and perhaps autologous) transplants. The viability of transplants, the ability of transplants to rescue overlying/neighboring photoreceptors, and the possibility of transplant proliferation, rejection or the development of proliferative vitreoretinopathy will be assessed with light and electron microscopy.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences C Study Section (VISC)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Medicine & Dentistry of NJ
Schools of Medicine
United States
Zip Code
Gullapalli, Vamsi K; Sugino, Ilene K; Van Patten, Yancy et al. (2005) Impaired RPE survival on aged submacular human Bruch's membrane. Exp Eye Res 80:235-48
Wang, Hao; Yagi, Fumihiko; Cheewatrakoolpong, Noounanong et al. (2004) Short-term study of retinal pigment epithelium sheet transplants onto Bruch's membrane. Exp Eye Res 78:53-65
Hansen, Kathleen A; Sugino, Ilene K; Yagi, Fumihiko et al. (2003) Adeno-associated virus encoding green fluorescent protein as a label for retinal pigment epithelium. Invest Ophthalmol Vis Sci 44:772-80
Wang, Hao; Ninomiya, Yoshihiko; Sugino, Ilene K et al. (2003) Retinal pigment epithelium wound healing in human Bruch's membrane explants. Invest Ophthalmol Vis Sci 44:2199-210
Leonard, Debra S; Sugino, Ilene K; Zhang, Xue-Guang et al. (2003) Ultrastructural analysis of hydraulic and abrasive retinal pigment epithelial cell debridements. Exp Eye Res 76:473-91
Sugino, Ilene K; Wang, Hao; Zarbin, Marco A (2003) Age-related macular degeneration and retinal pigment epithelium wound healing. Mol Neurobiol 28:177-94
Wang, H; Leonard, D S; Castellarin, A A et al. (2001) Short-term study of allogeneic retinal pigment epithelium transplants onto debrided Bruch's membrane. Invest Ophthalmol Vis Sci 42:2990-9
Castellarin, A A; Sugino, I K; Vargas, J A et al. (1998) In vitro transplantation of fetal human retinal pigment epithelial cells onto human cadaver Bruch's membrane. Exp Eye Res 66:49-67
Yao, R; Sugino, I K; Greulich, K M et al. (1998) Optimization of non-isotopic in situ hybridization: detection of the Y chromosome in paraformaldehyde-fixed, wax-embedded cat retina. Exp Eye Res 66:223-30
Leonard, D S; Zhang, X G; Panozzo, G et al. (1997) Clinicopathologic correlation of localized retinal pigment epithelium debridement. Invest Ophthalmol Vis Sci 38:1094-109