Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #147198
Title: OUTER SEGMENT PHAGOCYTOSIS BY CULTURED RETINAL PIGMENT EPITHELIAL CELLS REQUIRES GAS6

Author
item HALL, MICHAEL - UCLA
item PRIETO, ANNE - SCRIPPS RES INST
item OBIN, MARTIN - HNRCA
item ABRAMS, TOSHKA - UCLA
item BURGESS, BARRY - UCLA
item HEEB, MARY - SCRIPPS RES INST
item AGNEW, BRIAN - UC BERKELEY

Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/15/2001
Publication Date: 10/1/2001
Citation: N/A

Interpretive Summary: Growth arrest specific protein (GAS) 6 is a recently discovered vitamin K-dependent protein. Receptors for Gas6 are abundant in the brain, suggesting roles for Gas6 and by extension, vitamin K in maintenance or function of the nervous system. Mutation in a Gas6 receptor has recently been shown to cause retinal degeneration (blindness) in humans. This receptor, mertk, is required for the daily processing of "worn" photoreceptors (rods and cones) by the retinal pigment epithelial cells. This daily processing is absolutely required for maintaining the integrity of photoreceptors (rods and cones). We show for the first time that Gas6 can fully and selectively stimulate photoreceptor processing by the retinal epithelium. These results are the first demonstration of a function for vitamin K-dependent protein(s) in the healthy nervous system and suggest a role for vitamin K in the maintenance of retinal neurons.

Technical Abstract: The function and viability of vertebrate photoreceptors requires the daily phagocytosis of photoreceptor outer segments (OS) by the adjacent retinal pigment epithelium (RPE). We demonstrate here a critical role in this process for Gas6 and by implication one of its receptor protein tyrosine kinases (RTKs), Mertk (Mer). Gas6 specifically and selectively stimulates the phagocytosis of OS by normal cultured rat RPE cells. The magnitude of the response is dose-dependent and shows an absolute requirement for calcium. By contrast the Royal College of Surgeons (RCS) rat RPE cells, in which a mutation in the gene Mertk results in the expression of a truncated, non-functional receptor, does not respond to Gas6. These data strongly suggest that activation of Mertk by its ligand, Gas6, is the specific signaling pathway responsible for initiating the ingestion of shed OS. Moreover, photoreceptor degeneration in the RCS rat retina, which lacks Mertk, and in humans with a mutation in Mertk, strongly suggests that the Gas6/Mertk signaling pathway is essential for photoreceptor viability. We believe that this is the first demonstration of a specific function for Gas6 in the eye.