Duration of acidosis and recovery determine preretinal neovascularization in the rat model of acidosis-induced retinopathy

Abstract

Purpose. Systemic acidosis is a risk factor for retinopathy of prematurity (ROP). The present study tested the hypotheses that: a) a short period of acidosis is sufficient to produce neovascularization and b) recovery from acidosis is not needed for the development of preretinal neovascularization. Methods. Newborn Sprague-Dawley rats raised in 38 litters of 25 were randomly assigned within litters to 1, 3, or 6 days of acidosis, induced by twice daily gavage with NH 4 Cl (10mM/kg) beginning on the second day of life. Recovery time ranged from 0 to 15 days. All animals were raised in room air. Animals were sacrificed and retinal vasculature was assessed for preretinal neovascularization and retinal vascular areas. Results. Neovascularization occurred in up to 34% of rats exposed to 1 day of acidosis, 38% of rats exposed to 3 days of acidosis, and 55% of rats exposed to 6 days of acidosis. The incidence of neovascularization was maximal after 2 to 5 days of recovery regardless of the duration of NH 4 Cl exposure. However, recovery was not a requirement for the development of neovascularization. Conclusions. Periods of systemic acidosis as brief as 24 hours are associated with preretinal neovascularization in our newborn rat model of ROP using expanded litters. Systemic acidosis may damage the developing retinal vasculature and induce neovascularization, even without a period of recovery. A brief episode of systemic acidosis may be a risk factor for ROP in human neonates. Further attention should be directed to systemic acid-base balance in infants at risk for ROP.