Lipid Droplets May Protect Against AMD

Many cells in the body rely on lipids for a variety of purposes. They are building blocks of cell membranes, and play key roles in cell signaling, energy storage and transport. In the light-sensitive retina, two layers of cells—the retinal pigment epithelium (RPE) and the photoreceptors—exchange lipids as part of the process of turning light into an electrical signal that the brain interprets as vision.

Buildup of lipid in the RPE occurs naturally with age. But excessive lipid deposits outside the RPE form lipid-rich lesions—drusen and reticular pseudodrusen—which are early signs of age-related macular degeneration (AMD). AMD is the leading cause of irreversible blindness in the developed world.

As the RPE is a heavy consumer and producer of lipid, it temporarily stores some incoming lipid in structures called lipid droplets (LD). But little is known about what role LD may play in tasks like lipid metabolism, or whether or how LD might be employed to protect against the lipid-accumulations of drusen and reticular pseudodrusen seen in AMD.

Jason Miller, M.D., Ph.D., has been awarded a National Institutes of Health Mentored Clinical Scientist Research Career Development (K-08) award to begin filling in these gaps in understanding.

“Our premise is that, until now, science has been underestimating the role of lipid droplets as a protective mechanism in the RPE,” asserts Dr. Miller. “We hypothesize that rather than just ‘temporary storage’ for the RPE’s daily incoming lipid load, LD serve as versatile, dynamic regulatory hubs for lipid trafficking and metabolism.”

Miller will use a combination of imaging, biochemical assays, bio-energetic cell profiling and lipidomics to more fully describe RPE LD biology. Experiments will be performed on a combination of human adult RPE cultures and RPE cultures derived from induced pluripotent stem cells.

“Our hope is that shedding new light on the activities of LD in the RPE will point us to future therapeutic targets for AMD.”

Dr. Miller’s K-08 Mentor and Advisor Team:

Subramanium Pennathur, M.D., Professor and Chief of Nephrology; Director, O’Brien Kidney Translational Center; Director, Molecular Phenotyping and Metabolomics Core, Nutrition and Obesity Center

Ormond MacDougald, Ph.D., Professor of Molecular and Integrative Physiology; Professor of Endocrinology

Debra Thompson, Ph.D., Professor of Ophthalmology and Visual Sciences; Professor of Biochemistry

Sami Barmada, M.D., Ph.D., Professor of Neurology