Hepatocyte growth factor and its role in the pathogenesis of retinal detachment.
OBJECTIVE
Hepatocyte growth factor (HGF) regulates barrier function of retinal pigment epithelial (RPE) cells. The purpose of this study was to determine whether overexpression of HGF in the RPE induces retinal detachment (RD).


METHODS
E1/E3-deleted adenoviral vectors encoding HGF (Ad CMV.HGF), green fluorescent protein (Ad CMV.GFP), or connective tissue growth factor (AdCMV.CTGF) were injected subretinally in adult pigmented rabbits (5 x 10(4) plaque-forming units [pfu]/eye). Animals were observed for up to 28 days with fundus photography. HGF expression in the retina and vitreous was determined using immunohistochemistry, and ELISA. Histopathologic examinations were performed with light and electron microscopy.


RESULTS
Control eyes injected with AdCMV.GFP showed GFP expression almost exclusively in the RPE monolayer. Eyes injected with AdCMV.HGF showed strong HGF immunopositivity in RPE cells at the injection site. Elevated HGF levels were found in the vitreous peaking at postinjection day 7, diminishing to baseline by postinjection day 28. Eyes injected with AdCMV.HGF developed chronic RD and chronic inflammation in the choroid within the time frame of HGF expression. Groups of proliferating RPE cells were seen in the subretinal space in the region of the RD, and in some cases multilayered cellular membranes developed. No RD and minimal morphologic changes were seen in the eyes injected with AdCMV.GFP or AdCMV.CTGF.


CONCLUSIONS
Overexpression of HGF in RPE induces chronic, serous RD with subretinal proliferation of RPE. This work provides insight into the pathogenesis of RD and suggests that HGF should be further investigated as a target for therapeutic intervention in RD.
Jin
Manlin
M
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Chen
Youxin
Y
He
Shikun
S
Ryan
Stephen J
SJ
Hinton
David R
DR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055513:Connective Tissue Growth Factor; D003673:Defective Viruses; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D012163:Retinal Detachment / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014822:Vitreous Body / Q000378:metabolism
D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D055513:Connective Tissue Growth Factor; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor