Purchase this article with an account.
Y Chen, DA Leske, MP Fautsch, WL Lanier, JM Holmes; Acidosis-induced Retinopathy in the Neonatal Rat is Associated With VEGF . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1262.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously reported that metabolic acidosis can induce preretinal neovascularization (NV) in the neonatal rat, similar to retinopathy of prematurity (ROP). The molecular mechanisms involved in acidosis-induced retinopathy (AIR) are unknown. Since vascular endothelial growth factor (VEGF) has been implicated in oxygen-induced retinopathy and ROP, we investigated whether or not AIR is mediated by VEGF. Methods: The present study evaluated VEGF protein levels in the right (i.e., contralateral) retinae of rats described in a previous study of AIR (ARVO 2001). We had previously evaluated incidence and severity of NV in left retinae (ARVO 2001). Newborn Sprague-Dawley rats in litters of 25 were raised in room air and gavaged twice daily with NH4Cl (10 mM/kg body weight) for up to 6 days (from day 2 of life) followed by a period of recovery from 0 to 12 days. Additional rats in litters of 25 were assigned as non-gavaged controls. Animals were sacrificed on days 3, 5, 8, 10, 13 and 20 of life. Retinal VEGF protein expression was measured using ELISA (n=6 to 14 representative animals in each acidotic and control group). Retinal VEGF protein levels were compared between acidotic and control rats at each time point using Wilcoxon methods. Results: Retinal VEGF protein expression was decreased in acidotic rats compared to controls on day 3 (101.1 14.2 pg/mg vs 133.2 15.9 pg/mg; p=0.01) and increased in acidotic rats on day 8 (98.4 19.2 pg/mg vs 78.1 8.7 pg/mg; p=0.02). There were no significant differences on days 5, 10, 13, and 20. Conclusion: In our previous report of AIR (ARVO 2001), NV appeared at day 5 and was maximal at day 10. Presently, we report that, in the same animals, retinal VEGF protein is down-regulated during early acidosis exposure (i.e., day 3) followed by up-regulation (i.e. on day 8), immediately after the completion of the period of acidosis and just prior to the appearance of maximal NV. These data suggest that acidosis-induced retinopathy is associated with retinal VEGF levels and that NV may be VEGF mediated.
This PDF is available to Subscribers Only