Oxygen-induced retinopathy in the newborn rat: Morphological and immunohistological findings in animals treated with topical timolol maleate

Oxygen-induced retinopathy (OIR) similar to that seen in premature infants can be produced in newborn rats by exposure to 80% oxygen for the first 5 d ays of life, with subsequent recovery for 7 days in a room air environment. Previous studies have shown that the latter phase is associated with degen eration of retinal astrocytes. In the absence of astrocytes, the vascular e ndothelial growth factor (VEGF) is produced by the neurons of the inner ret ina. In this study, immunohistochemical met hods were used to assess retina l expression of VEGF protein in ratlings exposed to the above protocol, wit h and without simultaneous treatment with topical timolol maleate. Intraocu lar pressure (IOP) and arterial pressure were measured, The severity of OIR was also evaluated in retinal flat mounts after India ink perfusion. The m ean IOP was 8.25 +/- 0.32 mm Hg in untreated ratlings and 5.15 +/- 0.24 mm Hg in timolol-treated animals. OIR in retinas from the timolol group was le ss severe than that seen in untreated ratlings. VEGF protein expression was almost completely absent in the latter group. Retinas from timolol-treated animals expressed VEGF protein, though the level was inferior to that foun d in controls raised under room air conditions, in conclusion, these data s eem to indicate that experimental OIR can be attenuated by a reduction of t he IOP during and after oxygen supplementation. It is possible that these e ffects are due to improved ocular perfusion pressure, which would mitigate the hypoxic insult to the retina during the room air recovery period. Copyr ight (C) 2000 S. Karger AG, Basel.