We are interested in the phagocytic function of the retinal pigment epithelium (RPE) that is an important part of the circadian renewal of photoreceptor rod and cone outer segments in the retina. Every morning, each RPE cell phagocytoses and digests thousands of aged outer segment disks shed by photoreceptors. Since RPE cells do not turn over in the adult eye, each individual cell must clear its enormous phagocytic load efficiently every 24 hours over many decades. This activity renders RPE cells the most active phagocytes in the body. Deficiency or delay in the RPE?s ability to phagocytose shed outer segment particles contribute to devastating human blinding diseases, such as age-related macular degeneration, which affects millions of the elderly, and retinitis pigmentosa.

The long?term objective of our research is to understand the molecular mechanisms, which maintain the strict 24 hour rhythm of the phagocytic function of the RPE in the eye.
Ongoing projects are:

To unravel the individual contributions of plasma membrane receptors of RPE that play a role in clearance of shed outer segment particles (OS). These are the adhesion molecule avb5 integrin, the scavenger receptor CD36, and the receptor tyrosine kinase Mer. We characterize how lack of one or several of these phagocytic receptors affects RPE phagocytic activity and retinal function using mutant mice or rats.

To elucidate the cytosolic signaling pathways initiated by interaction of shed OS with RPE phagocytic receptors. Current work focuses on focal adhesion kinase and small GTPases of the Rho family.

To study how extracellular proteins secreted by photoreceptors or RPE regulate the daily phagocytic burst of RPE. Ongoing work includes the characterization of novel ligands for RPE phagocytic receptors in retina.


Email: sfinne@med.cornell.edu