Work in our laboratory is focused on understanding the cellular basis of retinal diseases like age-related macular degeneration (AMD), the most common cause of progressive vision loss among older adults worldwide. We study the retinal pigment epithelium (RPE), a monolayer of post-mitotic epithelial cells that forms the outermost layer of the retina and performs many functions that are indispensable for vision. It is now believed that over a lifetime, damage to the RPE coupled with genetic and environmental factors predispose a person towards developing AMD. However, AMD is a multifactorial disease, and elucidating the cascade of events that leads to vision loss has proven elusive. Our published work shows that RPE cells accumulate high levels of cholesterol under conditions that recapitulate certain features of AMD. Cholesterol homeostasis within cells is tightly controlled because excess cholesterol interferes with intracellular trafficking of proteins and lipids and inhibits basic housekeeping functions like lysosomal degradation, autophagy and secretion. Chronic disruption of these functions critically damages cell health.
Our current research has two main goals:
- to elucidate the pathogenesis of retinal degenerations at the cellular level using biochemistry, cell biology and high-speed live microscopy of healthy, aging and diseased RPE (from human donors, non-human primates, rodents and pigs)
- to use this information to identify novel drug targets and investigate whether existing drugs like statins can help preserve vision in the aging or diseased retina.