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L.E. Heathcote, I. Grierson, P. Hiscott, D. Wong, C. Groenewald; Hepatocyte Growth Factor (HGF) and Proliferative Vitreoretinal Disease . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2970.
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Purpose: Proliferative diseases, such as proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) are characterised by intraocular scar formation with concurrent retinal detachment (RD). HGF is associated with increased motility and scattering of a variety of epithelia, and also with a change in shape from epithelioid to a fibroblastic phenotype, similar to the epithelial to mesenchymal transition in the early stages of PVR. This study aimed to determine whether HGF levels in the vitreous are useful indicators for the development of proliferative disease after retinal detachment surgery and to establish whether these levels could initiate the cellular activities of scar formation. Methods: HGF concentrations in 77 vitreous specimens were determined using an ELISA assay. All statistical analyses were conducted using the Annova and independent T tests. HGF was applied at similar concentrations to those found in the vitreous to cultured human RPE cells in several bioassays. These bioassays included migration, proliferation, contraction and adhesion to extracellular matrix (ECM) proteins. Results: Patients developing proliferative vitreoretinal disease contained significantly higher levels (P<0.05) of HGF (PVR grade B 17.25 ± 9.10ng/ml, PVR grade C 19.72 ± 12.51ng/ml, PDR 18.52 ± 9.95ng/ml) than patients with uncomplicated RD (non proliferative control 9.16 ± 7.01ng/ml and rhegmatogenous RD 11.33 ± 6.21ng/ml). In vitro studies of RPE cells revealed significantly increased migration and proliferation at levels of 4ng/ml HGF and above, while HGF levels greater than 10ng/ml significantly increased contraction of collagen matrices. RPE settlement upon ECM proteins was not altered in the presence of HGF Conclusion: Vitreous levels of HGF were sufficient to initiate many of the key RPE activities associated with the early stages of proliferative retinal diseases, particularly migration and proliferation (HGF levels were greater than 4ng/ml in 96% of PVR specimens and in 71%, it was above 10ng/ml). Therefore, HGF may be bioactive in initiating the RPE cellular activities involved in PVR and be useful as an indicator of incipient proliferative disease.
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