Vanderbilt Center for Stem Cell Biology (VCSCB)

Research Description

The retinal pigment epithelium (RPE) is an essential epithelial monolayer interposed between the neural retina and the choroid. It supports both metabolic and cellular processes critical for function and homeostasis of the adjacent photoreceptors. RPE atrophy causes age-related macular degeneration (AMD), the leading cause of blindness in the elderly population. However, no effective cure for almost all AMD cases is currently available.

The RPE maintains tissue homeostasis through long-term survival, with little evidence of de novo cell production. Due to continued growth of the eye and aging, cell density decreases and RPE cells generally undergo hypertrophy. However, several lines of evidence suggest that certain subsets of the heterogeneous RPE cell population may contain distinct properties contributing to regenerative repair: the peripheral RPE displays enhanced proliferative capacity and human RPE contains a rare RPE population reminiscent of latent stem cells. In addition, animal models with robust healing capability, including mice, can regenerate RPE after chemically induced injury. Thus, we are determining ways to enhance proliferation combined with RPE differentiation to stimulate regenerative capacity. Our goal is to explore novel molecular regulators for promoting an intrinsic, regenerative response in the mature RPE and examine a potential subpopulation with regenerative capability in the adult RPE.

Another important focus in our lab is to obtain more insight into the gene regulatory networks, downstream effectors, and interaction between tissues and cells regulating early formation of the eye.  Congenital ocular malformations such as microphthalmia, anophthalmia, and coloboma (MAC) are prevalent in ~1 in 3-4,000 individuals and are the cause for over 25% of childhood blindness worldwide. The etiology of MAC in humans is complex and can result from disruption of several factors, however, we have limited knowledge to understand the complexity of these defects. One important process during eye formation is the coordinated growth of RPE and retina, for example reduced proliferation can result in small eyes (microphthalmia). Our efforts are to investigate fundamental mechanisms regulating growth and morphogenesis of during early stages of eye development.

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