CORNEAL ENDOTHELIAL REPAIR--ROLE OF LIPID MEDIATORS

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DESCRIPTION: The corneal endothelium exists as a monolayer of regularly arranged cells lining the posterior aspect of the cornea and maintains corneal transparency by removing fluid from the hydrophilic stroma, and the ability of this tissue to repair itself decreases with age. The PI goal is to determine how aging affects endogenously synthesized lipid mediators that play a key role in the functional recovery of the endothelium following injury. The corneal endothelium responds to bioactive lipids and actively regulates their endogenous synthesis and response pathways during the processes of mitosis, maturation and death. She proposes: 1)that LPA augments the limited mitotic capacity of the corneal endothelium, while 2)PGE2 promotes the development of the barrier function and 3) ceramide regulates acquisition of quiescence and apoptosis. To test these hypotheses, the PI proposes the following sets of studies: 1)Define the effects of lipid mediators on key steps in proliferation, differentiation and maturation; 2) Define the alterations in expression and distribution of the enzymes involved in the synthesis of PGE2, LPA and ceramide that occur in response to maturation; 3)Determine if the composition of membrane phospholipids changes as a result of age, proliferative status or injury; and 4)Test our prediction that adult human corneal endothelial cells exhibit the same profiles of LPA, PGE2 and ceramide as do mature culture of rabbit corneal endothelial cells. The outcome of these studies will suggest novel supplements (lipids, phospholipids, lipases) to corneal storage media and intraocular irrigation solutions which will promote functional recovery of traumatized and/or aged corneal endothelium.