May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Constitutive Activation of Hepatocyte Growth Factor Receptor Increases RPE Density and Heightens RPE Responses to Laser Injury
Author Affiliations & Notes
  • M. Kasaoka
    Schepens Eye Research Institute, Boston, Massachusetts
    Department of Opthalmology, Harvard Medical School, Boston, Massachusetts
  • F. Mo
    Schepens Eye Research Institute, Boston, Massachusetts
    Department of Opthalmology, Harvard Medical School, Boston, Massachusetts
  • K. Lashkari
    Schepens Eye Research Institute, Boston, Massachusetts
    Department of Opthalmology, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  M. Kasaoka, None; F. Mo, None; K. Lashkari, None.
  • Footnotes
    Support  U.S. Department of Defense
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3534. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: retinal pigment epithelium • wound healing • growth factors/growth factor receptors 
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