Morphological and functional evaluation of hESC-RPE cell transplantation in RCS rats

2015-07-15Age-related Macular Degeneration (AMD) is the leading cause of blindness among the elderly in United States. It is categorized into two types: neovascular (wet) AMD, caused by abnormal blood vessel growth in the choriocapillaris, and atrophic (dry) AMD, which is characterized by the extensive loss of retinal pigment epithelium, followed by the loss of photoreceptors. While several treatments are available for wet AMD, there is no effective way to address dry AMD. Although tablet formulation of select vitamins and minerals has been shown to slow the progression of dry AMD in some patients, there are currently no medical or surgical treatments. An effective therapy for dry AMD is needed. ❧ The purpose of this study is to evaluate the feasibility of using a cell based therapy to replace the dysfunctional retinal pigment epithelium (RPE), which is one of the contributing factors of AMD. The scientific evidence supporting such treatment comes from clinical studies using a surgical approach called macular translocation, in which the area with the diseased RPE is moved to an area with healthy RPE support. However, the surgery is complicated and carries a large risk of ocular complications, so it is rarely performed nowadays. The experiments outlined in this dissertation examined the feasibility of using an alternative approach by in vitro expansion of an RPE cell line derived from human embryonic stem cells. ❧ The specific aim of the study was to examine the functional outcome of transplantation of RPE cells in the dystrophic RCS rat by performing both in vivo functional examination and histological evaluation. The study also compared the outcome difference of cells delivered in different formats, either as a monolayer or a cell suspension. We evaluated the correlation of several non-invasive examinations and functional outcomes to see if these non-invasive techniques have the potential for predicting the treatment effects once the study moves to the human clinical trial. ❧ Our results showed that RPE transplantation as a monolayer had better visual function preservation compared to cell suspension injection and sham therapy. Histologic evaluation showed better preservation of retinal structure in animals transplanted with RPE monolayer. In vivo imaging showed correlation with the implant that may be translatable for future clinical evaluation of human clinical trials. Future studies will continue to develop the surgical technique in larger mammals for future application in human patients