Expression and significance of hypoxia-inducible factor-1α in retinal neovascularization induced by metabolic acidosis in newborn rats

Abstract

Objective To investigate the expression and significance of hypoxia-inducible factor-1a （HIF -1a） in the retinal neovascularization by metabolic acidosis in newborn rats. Methods One hundred and twenty newborn SD rats were randomly divided into acidosis （experiment） and normoxia （control） groups. A total of 60 newborn rats in experiment group underwent tubal feeding of NH4Cl at the dose of 535 mg/（kg · d） from the second day after birth, twice a day for 6 days and followed by a period of recovery. The rats in the two groups were sacrificed at the 3rd, 5th, 8th, 10th, 13th and 20th day after birth, respectively. The morphologic changes of retinal vessels were estimated by observing the vascular pattern in adenosine diphosphatase stained retina flat mounts. The newborn vessels were quantified by HE staining. Immunohistochemieal method was used to detect HIF-1a expression. Results In experiment group, numerous neovascufarization and un-perfused area at the periphery of vessels occurred on the 10th day. The result of HE staining showed that in experiment group of 10 day old, the number of neovascular nuclei extending into the vireo was 28. 78± 7.53, and that of the control group was 1.22 ±1.48 （t= 11. 169,P〈0. 01）. The results of immunohistochemistry revealed that the expression of HIF-1a protein were stronger in the experiment group than in the control group on the 8th, 10th and 13th day, and there were significant differences between the two groups （108. 87±15.21, 183. 68 ± 26.58 and 129.42 ± 9.85 vs 74.98±4.50, 76.38± 3.38 and 74.78±1.86, t=4.625, 9.023 and 9. 672,P〈0.05）. Conclusions HIF-1a might play an important role in retinal neovascularization. Key words: Retinal neovascularization; Hypoxia-inducihle factor 1, alpha subunit; Acidosis; Animals, newborn; Rats