applicat's abstract): The overall goal of this proposed research is to identify the cellular mechanisms involved in growth regulation of the corneal endothelium. The applicant and co-workers hypothesize that: (1) the growth of normal corneal endothelium is regulated by a membrane-associated regulatory complex (MARC), which is composed of tightly associated integral, structural and regulatory proteins; (2) disassembly of the MARC leads to proliferation and is mediated by intrinsic growth factors; and (3) that growth factors initiate disassembly directly through the MARC signaling pathways. This hypothesis will be tested using cat corneas. It is proposed to: (1) identify the specific subcellular localization of the MARC components in the normal cat; (2) determine the effect of intrinsic growth factors on the MARC organization and cell growth using a defined organ culture system; (3) determine whether the MARC organization can be modulated in vivo; and (4) to establish a growth factor/MARC signal transduction pathway. The proposed studies should provide new information regarding corneal endothelial growth and differentiation.
