Abstract
Abstract: :
Purpose: To determine the effects of H7 on retinal vascular permeability and electrophysiology at a concentration which increases outflow facility in monkeys. Methods: (1) Photopic, full-field electroretinograms (ERGs) were recorded for a range of flash intensities presented on a uniform white background of 9.15 ft-L to both eyes of 1 rhesus and 2 cynomolgus monkeys under isoflurane anesthesia. Multifocal ERGs (mERGs) also were recorded using an array of 103 equal-sized hexagonal elements presented to the central ±44 deg of the visual field. H7 (273.5µg/10µl cyno; 327.9µg/10µl rhesus) was administered as a bolus injection into the vitreous of one eye of each monkey so that the final concentration in the vitreous would be 300µM; vehicle was injected in the opposite eye. ERG and mERG responses were recorded beginning one hr post-H7 injection, and then hourly for 5 hr, at 24 hr, and 7 days post-injection. (2) H7 was given as above to one eye of 2 different cynomolgus monkeys under ketamine+diazepam anesthesia, and vehicle to the opposite eye. Three hr post-H7, 10% fluorescein (0.1ml/kg) was injected into the saphenous vein followed immediately by a fluorescein angiogram. Vitreous fluorescein levels were determined by fluorophotometry at 15 and 30 min, 1, 2, 3 and 4 hr post-fluorescein injection. Results: (1) Differential effects between H7 and control eyes were found neither in full-field ERGs nor first-order kernel mERG responses. (2) There was no difference in fluorescein angiograms between treated and control eyes and no abnormal leakage in either eye. After correcting for baseline, the fluorescein levels in the posterior and mid vitreous of the H7 eyes were not significantly higher when compared to contralateral controls. Conclusion: H7 at concentrations that increase outflow facility and reduce intraocular pressure does not appear to affect retinal electrophysiology or vascular permeability.
Keywords: 390 drug toxicity/drug effects • 396 electroretinography: non-clinical • 554 retina