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Valeria E Lorenc, Raquel Formica, Seth Fortmann, Peter A Campochiaro; Hepatocyte growth factor (HGF) induces vascular leakage in the retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5308.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effects of hepatocyte growth factor (HGF) on retinal vascular leakage and compare with leakage induced by vascular endothelial growth factor (VEGF)
Adult C57BL/6 mice were given an intravitreous injection of 0.5 µg (6.25 μM) HGF or 0.13 μg (6.25 μM) VEGF, or 0.5 µg HGF + 0.13 μg VEGF in one eye and PBS in the fellow eye. At 1 and 3 days after injection (n = 8 for each time point), the amount of albumin in the vitreous and retina was measured by ELISA. At 1 and 3 days after injection of 0.5 μg of HGF or PBS (n =5 for each time point), the level of mRNA for murine VEGF was measured by quantitative RT-PCR
Compared with fellow eyes injected with PBS, those injected with HGF had significantly more albumin in the vitreous (0.1 vs 0.06 µg/µl, p=0.01) and in the retina (0.009 vs 0.003 µg/µg, p=0.045) 1 day after injection. This difference was maintained, 3 days after injection (0.09 vs 0.07 µg/µl in the vitreous, p=0.02; and 0.007 vs 0.004 µg/µg in the retina, p=0.012). Interesting the injection of both growth factors together increased the albumin content in the vitreous 1 day after injection, compare with each growth factor by itself (0.64 vs 0.28 µg/µl compared to VEGF, p<0.001; and 0.64 vs 0.11 µg/µl compared with HGF, p<0.001). HGF was also capable of decreasing the VE-Cadherin protein levels in the retina 1 day after the injection (0.6 vs 0.4 OD VE-Cadherin/actin, p=0.02). Injections of HGF were not sufficient to modify VEGF mRNA levels in the retina compared with the fellow eyes injected with PBS (18241 vs 27932, at day 1; and 17267 vs 18142, at day 3, VEGF transcripts/106 cyclophillin A transcripts)
The injection of HGF alone was able to induce retinal vascular leakage, and when both growth factors were injected together a synergetic action between them occurred. HGF injections also induced a significant decrease in the protein levels of VE-Cadherin in the retina, without modifying the levels of VEGF mRNA. This data suggest that HGF may contribute with VEGF to increase the macular edema present in ischemic retinopathies
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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