Phototransduction in the Cones of Monkeys With Experimental Glaucoma and Optic Nerve Transection: Comparison With Multifocal ERG

Abstract

Abstract: : Purpose: To quantify cone receptor activity in non-human primates with experimental glaucoma and optic nerve transection (ONT) and to compare these measures with multifocal ERG (mfERG) responses. Methods: Two rhesus monkeys with unilaterally elevated intra-ocular pressure (IOP) following laser photocoagulation of the trabecular meshwork (LPTM) were followed for ~2.5 years. mfERG and full-field ERG testing were performed at monthly intervals over the last year. A third monkey underwent unilateral ONT. Following recovery, IOP was raised via LPTM in the transected eye. Average IOPs (mm Hg) of the experimental eye/fellow eyes were 29/16 (SD±10.6/2.8) and 33/15 (±10.6/3.9) for the intact animals and 33/17 (±11.6/3.1) in the ONT monkey. Photopic ganzfeld ERGs were obtained to a range of flash intensities presented on a rod-saturating background. The initial descending portion of the a-wave was fit with a version of the Lamb and Pugh model to estimate the maximal cone response (Rmax) and sensitivity (S) parameters. mfERG was recorded using a 103 element unscaled hexagonal array at standard 13.3 ms base rate. Results: As we have reported previously (ARVO 2002), chronic experimental elevation of IOP altered several aspects of the first-order mfERG waveform. Depression of a 40-70 ms component of the first-order mfERG was evident in experimental glaucoma and in animals with ONT. The implicit times of an early (N1) mfERG wave were also delayed or more variable in eyes with elevated IOP. Changes in the early mfERG wave also were correlated with the IOP variations over the course of the study. In contrast, the fitted parameters of the cone phototransduction model were not consistently altered in eyes with elevated IOP. Log Rmax and log S values were within the range reported in human and non-human primates. However, these measures did not vary with IOP on the day of test nor were there significant differences between eyes with elevated IOP when compared with fellow eyes. Conclusions: Histologic studies (Nork et al, Arch Ophthalmol 2000;18:235) have demonstrated patchy swelling of the L- and M-cones in human and experimental glaucoma. The results of the present study suggest that either these changes are not sufficiently diffuse to be detected by ganzfeld stimulation, or that cone phototransduction is generally unchanged and that the altered mfERG found reflects other aspects of glaucomatous pathology found in distal retina.

Keywords: electroretinography: non-clinical • retina: distal(photoreceptors, horizontal cell • animal model