Serial multifocal electroretinograms during long-term elevation and reduction of intraocular pressure in non-human primates

Abstract

The purpose of this study was to evaluate the relationship between elevations of intraocular pressure (IOP) and the multifocal electroretinogram (mfERG) in non-human primates. Experimental glaucoma was induced in 4 rhesus and 4 cynomolgus monkeys by laser trabecular meshwork destruction (LTD) in one eye. To evaluate the contribution of ganglion cells to mfERG changes, one monkey of each species had previously underwent unilateral optic nerve transection (ONT). After ≥ 44 weeks of elevation, the IOP was reduced by trabeculectomy in 2 non-transected animals. In the intact (non-transected) animals there was an increase in the amplitude of the early mfERG waveforms (N1 and P1) of the first order kernel (K1) throughout the period of IOP elevation in all of the rhesus, but not all of the cynomolgus monkeys. A species difference was also present as a decrease of the second order kernel, first slice (K2.1) in all of the cynomolgus monkeys but only in 1 of the rhesus monkeys (the 1 with the ONT). Similar IOP effects on the mfERG were seen in the ONT animals. Surgical lowering of IOP resulted in a return of the elevated K1 amplitudes to baseline levels. However, the depressed K2.1 RMS in the cynomolgus monkeys did not recover. These results demonstrate species-specific changes in cone-driven retinal function during periods of elevated IOP. These IOP-related effects can occur in the absence of retinal ganglion cells and may be reversible.

Functional and Anatomic Consequences of Subretinal Dosing in the Cynomolgus Macaque

“…The pre-injection baseline mfERG recordings showed some mild test-retest variability, which was within the previously described range for this species 36, 41, 42 . Not surprisingly, the mfERG responses from the region of retina corresponding to the subretinal bleb were markedly reduced immediately following the subretinal injection.…”

Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure

“…The three modes selected were mfERG, ff-ERG and PERG because they have each been evaluated extensively and proven effective in clinical studies of human glaucoma [19,21,13,14,22,23,20,24,15] as well as in previous laboratory studies in NHP eyes after retinal ganglion cell or optic nerve injury [34,28], including EG [35–39,17,40,41,29–31]. To our knowledge, however, no prior study has compared all three modes in the same cohort of glaucomatous eyes.…”

“…It remains unknown why the mfERG of the NHP seems to be relatively enriched with retinal ganglion cell contributions as compared to the human eye [49,55]. Indeed, this phenomenon might be even more specific to rhesus monkeys among primates [40]. …”

The effect of pentobarbital sodium and propofol anesthesia on multifocal electroretinograms in rhesus macaques

“…In early investigations within our laboratory, an IM injectable combination of ketamine/xylazine without paralysis did not provide sufficient ocular stabilization for acceptable recordings, although such an anesthetic combination has been applied successfully by other investigators [1-4]). In accompanying studies, the use of pentobarbital sodium anesthesia with mfERG and mfVEP recordings has resulted in a stable animal preparation and reproducible and robust functional results [11-12] [14] [20]. We also have anesthetized with a volatile inhalant (isoflurane) successfully [13] during electrophysiological recordings; however, with this anesthetic, experimental studies cannot be prolonged to avoid potential depression of the mfERG response [7].…”

“…Some of the studies [5-6] [8-10] have incorporated the use of a systemic neuromuscular blocker. Our laboratory has used pentobarbital sodium and isoflurane anesthesia without a paralytic agent in previous investigations of the multifocal electroretinogram (mfERG) [11-14] in rhesus and cynomolgus macaques.…”