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 days of life, with subsequent recovery for 7 days in a room air environment. Previous studies have shown that the latter phase is associated with degeneration of retinal astrocytes. In the absence of astrocytes, the vascular endothelial growth factor (VEGF) is produced by the neurons of the inner retina. In this study, immunohistochemical methods were used to assess retinal expression of VEGF protein in ratlings exposed to the above protocol, with and without simultaneous treatment with topical timolol maleate. Intraocular pressure (IOP) and arterial pressure were measured. The severity of OIR was also evaluated in retinal flat mounts after India ink perfusion. The mean 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 less 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 found in controls raised under room air conditions. In conclusion, these data seem to indicate that experimental OIR can be attenuated by a reduction of the IOP during and after oxygen supplementation. It is possible that these effects are due to improved ocular perfusion pressure, which would mitigate the hypoxic insult to the retina during the room air recovery period.
Ricci
B
B
Department of Ophthalmology, Catholic University, Roma, Italy.
Ricci
F
F
Maggiano
N
N
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007429:Intraocular Pressure / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D010100:Oxygen; D051381:Rats; D017208:Rats, Wistar; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013999:Timolol / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000319:Adrenergic beta-Antagonists; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013999:Timolol; D010100:Oxygen