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(Investigative Ophthalmology and Visual Science. 2002;43:483-489.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

PI3K and PLC{gamma} Play a Central Role in Experimental PVR

Yasushi Ikuno, Fee-Lai Leong and Andrius Kazlauskas

From The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

PURPOSE. It has been reported that the platelet-derived growth factor (PDGF)-{alpha} receptor ({alpha}PDGFR) is required for experimental proliferative vitreoretinopathy (PVR) in rabbits. This study investigated which of the signaling enzymes downstream of the {alpha}PDGFR participate in PVR.

METHODS. A panel of cell lines that expressed {alpha}PDGFR signaling mutants were made and characterized. These cell lines were used in a rabbit model of PVR and in an in vitro collagen type I contraction assay.

RESULTS. Phosphoinositide 3-kinase (PI3K) and, to a lesser extent, phospholipase C (PLC)-{gamma} were the signaling enzymes required for the {alpha}PDGFR to mediate PVR. Furthermore, the cells lines that were the most effective at inducing PVR displayed the most potent activity in the in vitro contraction assay.

CONCLUSIONS. PI3K and PLC{gamma} are necessary downstream effectors of the {alpha}PDGFR in experimental PVR. Consequently, these two signaling enzymes are required for one or more of the cellular responses (chemotaxis, proliferation, extracellular matrix production, contraction) that contribute to PVR.




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