Research | Fahim Lab

Choroideremia is an inherited blinding disease with no treatment. It shares some features with age-related macular degeneration (AMD), including slowly progressive degeneration of the retina and its blood supply, the choroid. We have developed choroideremia retinal pigment epithelial (RPE) cells using induced pluripotent stem cells derived from human blood. The choroideremia RPE cells demonstrate abnormal trafficking of proteins leading to altered cell metabolism and increased secretion of numerous proteins, some of which may damage surrounding cells. We hypothesize that changes in secreted proteins contribute to choroidal and retinal degeneration in choroideremia. Our research will identify specific pathways to develop future targeted therapies.

North Carolina Macular Dystrophy (NCMD) is an inherited retinal disease presenting in infancy with widely variable severity, from a few small retinal deposits called drusen and no visual symptoms to a large central retinal defect, or coloboma, causing a central blind spot and legal blindness. NCMD is caused by whole-gene duplications and single nucleotide variants in the gene PRDM13, which encodes a zinc finger transcription factor. Our research aims to identify downstream effects of PRDM13 overexpression on differentiation and function of the retina and retinal pigment epithelium (RPE) in North Carolina Macular Dystrophy. 

RPE cells sit between the retina and the blood supply called the choroid and secrete growth factors and cytokines in both directions. Numerous RPE secreted proteins have been linked to the pathogenesis of age-related macular degeneration (AMD). Oxidative stress is an important contributing factor causing AMD, and we have used chemically induced oxidative stress in RPE cell culture as a model of AMD. Oxidative stress altered the secretion of multiple factors implicated in AMD and additional studies are ongoing to investigate chronic oxidative stress and secretion of proteases, or molecular scissors that break down the scaffolding that holds cells together, to identify future therapeutic targets for this common blinding disease.