Metabolic acidosis-induced retinopathy in the neonatal rat

Jonathan M. Holmes, Shuichen Zhang, David A. Leske, William L. Lanier

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

PURPOSE. Carbon dioxide (CO2)-induced retinopathy (CDIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), was previously described by our group. In this model, it is possible that CO2- associated acidosis provides a biochemical mechanism for CDIR. Therefore, the effect of pure metabolic acidosis on the developing retinal vasculature of the neonatal rat was investigated. METHODS. A preliminary study of arterial blood pH was performed to confirm acidosis in our model. In neonatal rats with preplaced left carotid artery catheters, acute blood gas samples were taken 1 to 24 hours after garage with either NH4Cl 1 millimole/100 g body weight or saline. In the subsequent formal retinopathy study, 150 newborn Sprague-Dawley rats were raised in litters of 25 and randomly assigned to be gavaged twice daily with either NH4Cl 1 millimole/100 g body weight (n = 75) or saline (n = 75) from day 2 to day 7. After 5 days of recovery, rats were killed, and retinal vasculature was assessed using fluorescein perfusion and ADPase staining techniques. RESULTS. In the preliminary pH study, the minimum pH after NH4Cl garage was 7.10 ± 0.10 at 3 hours (versus 7.37 ± 0.03 in controls, mean ± SD, P < 0.01). In the formal retinopathy study, preretinal neovascularization occurred in 36% of acidotic rats versus 5% of controls (P < 0.001). Acidotic rats showed growth retardation (final weight 16.5 ± 3.0 g versus 20.2 ± 2.6 g, P < 0.001). The ratio of vascularized to total retinal area was smaller in acidotic rats (94% ± 4% versus 96% ± 2%, P < 0.001). CONCLUSIONS. Metabolic acidosis alone induces neovascularization similar to ROP in the neonatal rat. This suggests a possible biochemical mechanism by which high levels of CO2 induce neovascularization and supports the suggestion that acidosis may be an independent risk factor for ROP.

Original languageEnglish (US)
Pages (from-to)804-809
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume40
Issue number3
StatePublished - Mar 11 1999

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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