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M. Kasaoka, F. Mo, K. Lashkari; Constitutive Activation of Hepatocyte Growth Factor Receptor Increases RPE Density and Heightens RPE Responses to Laser Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3534.
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RPE cell migration and transdifferentiation play an integral role in retinal responses to laser injury. We assessed whether constitutive activation of the hepatocyte growth factor receptor HGFR/cMet leading to its overactivation can affect RPE morphology and its response to laser injury.
C57BL/6 mice and FVB/N-Tg/mtTPRmet mice (expressing constitutively active form of HGFR/cMet) were treated with retinal diode laser photocoagulation and were sacrificed at intervals ranging between 3 hr and 14 days. At each time point retinas and eyecups were subjected for qRT-PCR to detect mRNA expression of HGF and HGFR/cMet. To confirm laser spots, DAPI and TUNEL staining were used to detect apoptosis cells. Immunohistochemistry for HGF and HGFR/cMet was performed after bleaching melanin pigment.
mRNA expression of HGF and HGFR/cMet mRNA in laser-treated retina were significantly increased at all time points as compared to sham injury, peaking at 3 hours and 12 hours for HGF and HGFR/cMet, respectively. FVB/N-Tg/mtTPRmet mice expressed increased RPE and inner choroidal density compared with control littermates and C57BL/6 mice. Expression of HGFR/cMet was also increased in both RPE and the inner choroidal layers. In response to laser injury, FVB/N-Tg/mtTPRmet mice exhibited more robust pigment migration into the retina.
HGF - HGFR/cMet receptor system is intimately involved in RPE wound healing responses after laser injury. Constitutive activation of HGFR/cMet induces morphological changes in the RPE and choroidal layers and enhances RPE responses to laser injury including migration and transdifferentiation. Control of HGFR activity may be a future therapeutic target to minimize retinal damage after laser injury.
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