Jie Gong, M.D., Ph.D.
SUMMARY OF LABORATORY RESEARCH
Age Related Macular Degeneration (AMD) is the leading cause of blindness over the age of 55, affecting 30-50 million people globally. Despite several advances over the last decade, there are significant limitations to treatments available for patients with advanced geographic atrophy (GA) which is characterized by a complete loss of the retinal pigment epithelium (RPE) and degeneration of photoreceptors. In patients with advanced GA, restoration of vision will require transplantation of new RPE into the bed of atrophy. Stem cells are an excellent source of cells for replacement therapy given the limited reservoir of donor cells for RPE transplantation strategies, lack of regeneration of photoreceptors, and variation in success of autografts. The overall goal of my work is to develop techniques and tools that allow for the generation of RPE and/or retinal photoreceptors cells from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs).
Projects focus on the identification and use of extracellular matrix (ECM) to direct stem cell differentiation into retinal neurons or RPE cell lineage. Previous study in our laboratory has shown that human Bruch’s membrane can direct differentiation of stem cells toward a RPE and/or photoreceptor fate. Techniques that allow for the combining of transcription factors involved in RPE/photoreceptor development with ECM factors to influence the differentiation of stem cell into a neuronal fate will be applied. The identification of ECM proteins may also assist future scaffold design to support the differentiation and maintenance of RPE.On a cellular level, AMD is characterized by cellular changes in the RPE, choriocapillaris and outer retina, and by structural changes in basement membrane (BM). These changes in BM disease may cause some of the pathology that occurs in advanced AMD, including cell atrophy and the development of choroidal neovascularization. I am also engaged in determining the effects of age-related changes within BM on the biology of the RPE cells (RPE cell survival, reattachment, phagocytosis effect and retinal retinoid metabolism) through the use of organ culture of post-mortem donor retinas. Development of techniques and tools that direct stem cell differentiation can improve the outcome of cell-based therapy for the treatment of AMD.