Functional evaluation of retina and optic nerve in the rat model of chronic ocular hypertension

Purpose. To functionally characterize the rat retina and optic nerve after chronic elevation of the intraocular pressure (IOP) using electroretinography (ERG) and computerized pupillometry. Methods. Chronic elevation of the IOP was induced in Brown Norway rats by combined injection of indocyanine green dye (ICG) into the anterior chamber and diode laser treatment, followed by ERG and pupil light reflex (PLR) monitoring. Results. Laser treatment induced significant elevation of the IOP in operated eyes for 6 weeks, with maximal values observed 14 days postoperatively (ctrl = 18(.)4 +/- 2(.)4 and operated = 35 +/- 8(.)4 mmHg; mean +/- sD). Preoperative values for the PLRratio were 68(.)5 +/- 4% (mean +/- SEM; %). Three days postoperatively the PLRratio decreased to 60(.)3 +/- 10(.)3%, but was not significantly different compared to preoperative values (p > 0(.)05, Kruskal-Wallis non-parametric test with Dunn's post-test). However, 7, 14 and 21 days postoperatively the PLR function dramatically decreased to 14(.)6 + 8(.)6, 11(.)5 +/- 6(.)7 and 12(.)6 +/- 4%, respectively, and was significantly smaller compared to preoperative values (p < 0(.)01). At day 28 the PLR significantly recovered and was not significantly different compared to preoperative values (PLRratio = 38(.)5 +/- 8(.)6, p > 0(.)05). However, 35 days after surgery the PLR started to decrease once again in the operated eyes (PLRratio = 17(.)2 +/- 7(.)4%) and was significantly smaller again compared to preoperative values (p < 0(.)05). The PLR values continued to decrease until the end of experiment (60 days postoperatively). ERG analysis of operated eyes revealed significantly decreased amplitudes of a- and b-waves 10d postoperatively, while oscillatory potentials (OPs) and flicker ERG (flERG) amplitudes were not detectable. However, 28 days postoperatively OPs significantly, but temporarily recovered, while a-wave, b-wave and flERG amplitudes did not significantly change compared to values observed 10d postoperatively. The ERG analysis of the operated eyes revealed significantly reduced amplitudes 60 days postoperatively. Histological analysis revealed degeneration of all retina layers and optic nerve axons. Conclusions. Chronic ocular hypertension in rats produces dramatic damage to all retinal layers and optic nerves observed by morphological and functional methods which significantly correlate with the IOP elevation. Outer retina of glaucomatous rats seems to be more susceptible to the damage due to chronic elevation of the IOP. Chronic hypertensive rat eyes have capacity to temporarily recover function of the inner retina and optic nerve. (C) 2004 Elsevier Ltd. All rights reserved.