Abstract
TNF-α has been found in the retina. Hyperoxia and hypoxia regulate TNF-α expression. TNF-α is an important factor in inflammation and angiogenesis. Dexamethasone inhibits TNF-α production. Changes in TNF-α expression in the retina may play an important role in the development of oxygen-induced retinopathy. Oxygen-induced retinopathy was produced in C57BL6 mice by exposure to 75% oxygen at Postnatal Day 7 (P7) for 5 days and the mice recovered in room air until Day 17 (P17). Dexamethasone was administered at 0.5 mg/kg/day once daily subcutaneously during the 5 days of oxygen exposure. TNF-α expression was evaluated at Day 7 prior to oxygen exposure, at Day 12 (P12) immediately upon removal from oxygen, and at Day 17, the time of maximal vasoproliferation by RT-PCR. TNF-α is developmentally regulated in the retinae of C57BL6 mice. From P7 to P12, there is a 3-fold increase in TNF-α expression and from P7 to P17 there is a 2.7-fold increase. There was 2.7-fold suppression in expression immediately following oxygen exposure at P12. The expression was dramatically increased at P17, the time of maximal vasoproliferation. Dexamethasone inhibited the expression of TNF-α at P17 by 6.4-fold. At this dose, it also suppressed the baseline TNF-α expression in the mouse model. In summary, TNF-α is altered in the development of oxygen-induced retinopathy in the mouse. It increased markedly during the vasoproliferative phase and was suppressed by dexamethasone. Modulation of TNF-α expression may provide a potential site of action for future therapeutic targets.