Effect of raised inspired carbon dioxide on the incidence and severity of neovascularization in a rat model of retinopathy of prematurity

J. M. Holmes, D. A. Leske, L. A. Duffner

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. Current rat models of retinopathy of prematurity (ROP) use fluctuating hyperoxic/hypoxic environments to induce neovascularization. ROP may develop in human infants without raised pO2, therefore raised pCO3 has been suggested as a risk factor. We investigated the effect of raised inspired CO2 on oxygen induced retinopathy in the rat. Methods. 100 newborn Sprague-Dawley rats were exposed to 7 days of 80% O2. Once each day, inspired O2 was reduced to 10% for 30 mins and returned to 80% O2 over 3hrs. 50 of the rats were also exposed to continuous high CO2 (6.0% ± 0.1% SD) during O2 exposure and 50 to low CO2 (0.3% ± 0.1%). After a further 5 days in room air, all rats were sacrificed after intracardiac injection of fluorescein under deep anesthesia. The retinas were dissected and flat mounted for ADPase staining and fluorescent microscopy. The presence and number of clock hours of abnormal neovascularization were evaluated in a masked manner and the ratios of vascularized:total retinal area were calculated using computer assisted image analysis. Chi-square, Mann-Whitney U tests, ANOVA and Spearman rank correlation were used for analysis. Results. Neovascularization occurred in 80% of rats exposed to high CO2 vs 52% exposed to low CO2 (p=0.02). The median severity was greater in rats exposed to high CO2 (median 3 clockhrs vs 1, p=0.01). The ratio of vascularized:total retinal area was smaller in rats exposed to high CO2 (80% ± 14% vs 89% ± 5%, p=0.02), and the severity of neovascularization was inversely correlated to this ratio (r= -0.6, p<0.001) Conclusions. Elevated inspired CO2 increases the incidence and severity of abnormal neovascularization in a rat model of ROP. This may further support a role or raised pCO2 in the development of ROP.

Original languageEnglish (US)
Pages (from-to)S127
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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