Abstract
Abstract: :
Purpose: To determine the association between functional retinal vasospasm (defined as inappropriate vasoconstriction during a carbogen challenge) and NV in a newborn rat model of retinopathy of prematurity (ROP). Methods: Newborn rats were raised under two variable oxygen conditions (50/10 or 40/15) for 14 days and then allowed to recover in room air. Functional magnetic resonance imaging was used to determine the retinal oxygenation response (ΔPO2, mm Hg) to hyperoxic inhalation challenges. Evidence for functional vasospasm was determined by comparing panretinal ΔPO2 measured during carbogen and 100% oxygen breathing. In control rats, carbogen-induced ΔPO2 are greater than oxygen-induced changes so similar ΔPO2 measured in experimental rats during carbogen and oxygen breathing is considered evidence for functional vasospasm. ADPase stained retinas were analyzed to determine the NV incidence and severity. Results: As expected, the 40/15 procedure produced significantly (P < 0.05) lower NV incidence and severity (8 % (7/91), median 1 clockhour) than the 50/10 protocol (100% (122/122), 6 clockhours). At day 20, retinal ΔPO2 during carbogen breathing of the 40/15 animals that did not have evidence of NV was not different (P > 0.05) from that of normal age-matched animals (138 + 6 mm Hg, n = 13, mean + SEM vs. 130 + 5 mm Hg, n = 11, respectively). At day 26 and 34, retinal ΔPO2’s during carbogen breathing of the 50/10 rats that no longer had NV (84 + 4 mm Hg, n = 5 and 87 + 3 mm Hg, n = 7 respectively) were significantly (P < 0.05) lower than that of age-matched control pups (145 + 5 mm Hg, n = 5 and 136 + 6 mm Hg, n = 5 respectively). In separate experiments, at day 34, retinal ΔPO2’s during oxygen breathing of the control rats (94 + 45 mm Hg, n = 7), but not in 50 /10 rats (99 + 3 mm Hg, n = 9), were significantly (P < 0.05) different from the carbogen breathing values (136 + 6 mm Hg and 87 + 3 mm Hg, respectively). Conclusions: No evidence for functional vasospasm was found in 40/15 rats that did not develop NV by P20; later time points were not examined. This result, together with our previous data in 50/10 rats of a subnormal retinal ΔPO2 before and during NV, support an association between vasospasm and the development of NV. In the current study, in 50/10 rats, functional vasospasm persisted after regression of the retinal NV suggesting a continuation of risk of developing additional retinal complications after resolution of the NV in ROP.
Keywords: animal model • imaging methods (CT, FA, ICG, MRI, OCT, RTA, S • retinal neovascularization