Abstract 414

Purpose: Postnatal corticosteroids have been reported to have deleterious, protective, and no effect on retinopathy of prematurity. Conflicting results may be due to timing of steroid administration. The goal of this study was to determine effects of early and late postnatal dexamethasone on retinopathy in a mouse model.

Methods: The C57BL6 mouse model of oxygen-induced retinopathy (by placing animals in 75% oxygen from day 7 to day 12) was used to create retinal neovascularization. Dexamethasone 0.5 mg/kg/day was administered from day 1 to day 5 in the early group. The late group received five days of dexamethasone at the same dose beginning on day 12. Mice were sacrificed at day 17-21, and retinal vasculature was assessed by a retinal scoring system of whole mount preparation following high molecular-weight fluorescein-labeled dextran perfusion. In addition, retinal neovascularization was assessed by quantification of extraretinal neovascular nuclei in the retinal section. Statistical significance was defined as p < 0.05 and was determined by the Kruskall Wallis test, Mann Whitney tests, and Student t tests.

Results: Animals exposed to oxygen who received early dexamethasone had an improvement in retinopathy (C = control, ED = early dexamethasone, LD = late dexamethasone, and O = oxygen). (Table) Median retinopathy score is represented as SCORE [median (25th-75th quartile)] and the number of neovascular nuclei are represented by NUCLEI (mean ± standard deviation). * denotes p < 0.05 when compared to oxygen treatment. There was significant growth retardation observed in the early and late dexamethasone treated animals (∝designates p < 0.05) when compared to control animals. Animal number is designated by n.

Table 1 No caption available
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Conclusions: Timing of dexamethasone administration is critical to the inhibition of development of retinopathy in the mouse model. Degree of growth retardation also appeared to be timing dependent. These data may explain the different results of clinical observations with respect to corticosteroid treatment, timing, and development of retinopathy.

Funded by Fight for Sight-Prevent Blindness America (GA98-005).