c-Met modulates RPE migratory response to laser-induced retinal injury.
Retinal laser injuries are often associated with aberrant migration of the retinal pigment epithelium (RPE), which can cause expansion of the scar beyond the confines of the original laser burn. In this study, we devised a novel method of laser-induced injury to the RPE layer in mouse models and began to dissect the mechanisms associated with pathogenesis and progression of laser-induced RPE injury. We have hypothesized that the proto-oncogene receptor, c-Met, is intimately involved with migration of RPE cells, and may be an early responder to injury. Using transgenic mouse models, we show that constitutive activation of c-Met induces more robust RPE migration into the outer retina of laser-injured eyes, while abrogation of the receptor using a cre-lox method reduces these responses. We also demonstrate that retinal laser injury increases expression of both HGF and c-Met, and activation of c-Met after injury is correlated with RPE cell migration. RPE migration may be responsible for clinically significant anatomic changes observed after laser injury. Abrogation of c-Met activity may be a therapeutic target to minimize retinal damage from aberrant RPE cell migration.
Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
Masataka
M
Kasaoka
Jie
J
Ma
Kameran
K
Lashkari
D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000201:enzymology / Q000473:pathology; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D019426:Integrases / Q000378:metabolism; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000201:enzymology* / Q000293:injuries* / Q000473:pathology
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C045073:Cre recombinase; D019426:Integrases