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The effect of raised inspired carbon dioxide on developing rat retinal vasculature exposed to elevated oxygen
J M Holmes1, L A Duffner, J C Kappil
1Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60513.
Insights
Elevated carbon dioxide (CO2) levels significantly hinder retinal vascular development in newborn rats exposed to fluctuating oxygen. This finding suggests CO2 may be a risk factor for retinopathy of prematurity in infants.
Area of Science:
- Ophthalmology
- Neonatology
- Physiology
Background:
- Hyperoxia is a known risk factor for retinopathy of prematurity (ROP), a leading cause of blindness in premature infants.
- ROP can also develop in infants with low oxygen levels, such as those with cyanotic congenital heart disease, suggesting other factors like elevated carbon dioxide (pCO2) may play a role.
Purpose of the Study:
- To investigate the impact of inspired carbon dioxide (CO2) on oxygen-induced retinopathy in a rat model.
- To determine if elevated CO2 exacerbates or modifies the effects of fluctuating oxygen on retinal vascular development.
Main Methods:
- Newborn Sprague-Dawley rats were exposed to cyclical high oxygen for seven days.
- Two groups were established: one with negligible CO2 (control) and one with elevated inspired CO2.
- Following oxygen exposure, rats underwent a three-day recovery period in room air before retinal analysis using fluorescein and microscopy.
Main Results:
- Rats exposed to elevated inspired CO2 showed significantly reduced retinal vascularization (62% +/- 7% SD) compared to the control group (81% +/- 7% SD).
- The difference in vascularization between the high CO2 and low CO2 groups was statistically significant (p < 0.001).
Conclusions:
- Elevated inspired CO2 significantly retards retinal vascular development in neonatal rats exposed to fluctuating hyperoxia.
- These findings suggest that elevated CO2 levels may be a critical contributing factor to the development of retinopathy of prematurity, particularly in cases without hyperoxia.
Abstract:
Hyperoxia is a risk factor for retinopathy of prematurity (ROP), a blinding disease in infants. However, ROP develops in human infants without raised arterial oxygen levels, such as in cyanotic congenital heart disease. In these infants raised pCO2 may be a risk factor. We investigated the effect of inspired CO2 on oxygen induced retinopathy in the rat. 56 newborn Sprague-Dawley rats were exposed to high cyclical O2 for seven days. In a control group, 27 rats were exposed to negligible CO2 by the use of soda lime. In the high CO2 group, 29 rats were exposed to elevated CO2 by omitting soda lime from their chambers. Rats in both groups had a recovery period of three days in room air following cyclical O2 exposure. On the eleventh day all rats were sacrificed after intracardiac injections of fluorescein under deep anesthesia and the retinae were dissected and flat mounted for fluorescent microscopy. The ratio of vascularized:total retinal area was calculated using computer assisted image analysis. In the high CO2 group 62% +/- 7% SD of the retina was vascularized vs. 81% +/- 7% in low CO2 group (p < 0.001). Elevated inspired CO2 results in pronounced retardation of retinal vascular development in neonatal rats exposed to fluctuating raised oxygen.