The Effect Of Latrunculin–B On Retinal Physiology

Abstract

Abstract: : Purpose: To determine the effects of Latrunculin–B (Lat–B) on retinal vascular permeability and electrophysiology at a concentration that has been shown to enhance outflow facility in the cynomolgus monkey. Methods: (1) Lat–B (1.98mg/10ml) was given as a bolus injection into the mid–vitreous of one eye of 4 cynomolgus monkeys under ketamine+diazepam or ketamine+medetomidine anesthesia so that the final concentration in the vitreous was 2.0mM; vehicle (100% DMSO) was given to the opposite eye. Three hrs post–Lat–B, 10% fluorescein (0.1 ml/kg) was administered into the saphenous vein, immediately followed by fluorescein angiograms in 2 of the monkeys. Vitreous fluorescein levels were measured by fluorophotometry in all 4 monkeys immediately prior to, 15 min, 30 min, and 1, 2, 3, and 4 hrs after IV fluorescein. (2) Photopic, full–field electroretinograms (ffERGs) were recorded for a range of flash intensities presented on a uniform white background of 9.15 ft–L to both eyes of 2 cynomolgus monkeys under isoflurane anesthesia. Multifocal (mERGs) also were recorded using an array of 103 equal–sized hexagonal elements presented to the central ±44 deg of the visual field. Lat–B was administered as above to one eye of each monkey; vehicle to the opposite eye. ffERG and mERG responses were recorded at baseline, 4 hrs, 48 hrs, and 7 days post– Lat–B injection. Results: (1) Fluorescein levels in the posterior and mid–vitreous of Lat–B eyes were not significantly higher than levels in contralateral control eyes at any time point. There was no abnormal leakage in either treated or control eyes as evident by fluorescein angiogram. (2) There was no difference in the photopic full–field ERG or the first–order kernel multifocal ERG when comparing Lat–B treated to contralateral control eyes at any time point. Conclusions: Lat–B at concentrations that increase outflow facility and reduce intraocular pressure does not appear to affect retinal electrophysiology or retinal vascular permeability.

Keywords: retina • drug toxicity/drug effects • electrophysiology: non–clinical