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J.R. McColm, P. Geisen, M.E. Hartnett; Exogenous Leukemia Inhibitory Factor Attenuates Retinal Vascularization in Rat . Invest. Ophthalmol. Vis. Sci. 2005;46(13):573.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Previous studies have shown that transgenic mice that overexpress LIF in their lens have no retinal vasculature. We wished to test whether exogenous LIF affected rat retinal vascular development. Methods: p3 Sprague–Dawley rats were given either an intraperitoneal (IP) injection of LIF (100ng/0.1ml) or PBS and analysis performed at p6 (p3/6). p7 rats were given an intravitreous (IV) injection of LIF (5ng/1ul) or PBS (1ul) and analysis performed at p9 (p7/9). At time of analysis animals were euthanized, eyes removed and retinas flatmounted. Retinas were stained with Griffonia lectin and activated caspase–3. The retinal peripheral avascular area was measured and expressed as percent of total retinal area, and number of apoptotic cells counted. Results: LIF injected either IP or IV had no effect on body weight or total retina area, but significantly increased the peripheral retinal avascular area. Mean peripheral retinal avascular area ± SD: p3/6 PBS injected 36.8% ± 5.8 vs LIF–injected 39.7% ± 5.5, p<0.045 T–test. p7/9 non–injected 4.7% ± 3.8, PBS–injected 5.7% ± 3.3 and LIF injected 9.1% ± 4.4, p<0.0001 ANOVA; LIF–injected significantly different from both non–injected at p<0.0001 and PBS injected at p<0.022, Bonferroni correction. In the p3/6 group no difference was seen in the number of apoptotic cells between PBS– or LIF–injected groups. In the p7/9 group, the injected eyes both had significantly more apoptosis than the non–injected (ANOVA was significant at p<0.0001. Post hoc testing with the Bonferroni correction PBS–injected p=0.001 and LIF–injected p=0.0001 both compared to non–injected.) Conclusions: LIF blocks retinal vascular development in vivo but this does not appear to be through apoptosis of endothelial cells.
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