PI3K and PLCgamma play a central role in experimental PVR.
OBJECTIVE
It has been reported that the platelet-derived growth factor (PDGF)-alpha receptor (alphaPDGFR) is required for experimental proliferative vitreoretinopathy (PVR) in rabbits. This study investigated which of the signaling enzymes downstream of the alphaPDGFR participate in PVR.


METHODS
A panel of cell lines that expressed alphaPDGFR 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 alphaPDGFR 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 PLCgamma are necessary downstream effectors of the alphaPDGFR 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.
Ikuno
Yasushi
Y
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Leong
Fee-Lai
FL
Kazlauskas
Andrius
A
D000818:Animals; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051966:Phospholipase C gamma; D011233:Precipitin Tests; D011817:Rabbits; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology*; D018630:Vitreoretinopathy, Proliferative / Q000201:enzymology*
D024042:Collagen Type I; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D010738:Type C Phospholipases; D051966:Phospholipase C gamma