Carbon dioxide-induced retinopathy in the neonatal rat.
OBJECTIVE
Hypercarbia has been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of hypercarbia on the retinal vasculature of the neonatal rat to determine whether hypercarbia alone could induce preretinal neovascularization analogous to ROP.


METHODS
In a preliminary blood gas study, 8-11-day-old rats were exposed to specific levels of inspired O2 and either 0.2% CO2 or 10% CO2. Arterial blood gases were obtained, and a level of inspired O2 was determined that, when combined with inspired 10% CO2, would produce a PaO2 equivalent to room air (pure hypercarbia). In the formal retinopathy study, 300 newborn rats raised in 12 expanded litters (n = 25 each) were exposed for 7 days to either room air, 10% CO2 in 21% O2 and nitrogen (high-inspired CO2 group) or 10% CO2 in 12.5% O2 and nitrogen (pure-hypercarbia group). Each type of exposure was followed by recovery in room air for 5 days. Animals were sacrificed on day 13 and retinae were analyzed, using fluorescein perfusion and ADPase staining techniques.


RESULTS
Neovascularization occurred in 19% of rats in the high-inspired CO2 group, and 14% of rats in the pure-hypercarbia group, compared to 0% of rats exposed to room air alone (p = 0.001, Chi square).


CONCLUSIONS
In the neonatal rat model, exposure to hypercarbia alone, followed by room air recovery, results in preretinal neovascularization similar to that seen in oxygen-induced retinopathy. Our results support the suggestion that hypercarbia may be a risk factor for retinopathy of prematurity.
Holmes
J M
JM
Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA. holmes.jonathan@mayo.edu
Zhang
S
S
Leske
D A
DA
Lanier
W L
WL
D000818:Animals; D000831:Animals, Newborn; D001081:Apyrase / Q000378:metabolism; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000008:administration & dosage*; D006801:Humans; D006935:Hypercapnia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D018496:Hyperoxia / Q000150:complications; D007231:Infant, Newborn; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012171:Retinal Vessels / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors
D002245:Carbon Dioxide; D001081:Apyrase