Idiopathic bilateral optic atrophy in the rhesus macaque

METHODS. In vivo assessment of retinal and optic nerve structure included fundus biomicroscopy and stereophotography. Functional analyses included transient pattern-reversal electroretinography (PERG) and full-field flash ERG, with both white flashes while dark adapted and red flashes on a blue background used to assess the photopic negative response (PhNR). Also measured were visual evoked cortical potentials (VEPs) and multifocal (mf)ERGs, with both a standard fast and slowed (7F) stimulation sequence. Post mortem histologic evaluation was performed on a subset of five animals with BOA and compared with data from 22 healthy normal animals. Blood tests, including vitamin E, B12, folate, lead, and complete blood cell count with differential were obtained on the four animals that remained alive. RESULTS. Animals with BOA showed temporal pallor of the optic nerve head and thinning of the retinal nerve fiber layer (RNFL) between the temporal vascular arcades (i.e., of the papillomacular bundle). Severity of optic atrophy and RNFL loss varied between animals from mild to severe, but was similar in the two eyes of each animal. Functional changes included greater loss of the PERG N95, compared with the P50 component and substantial reduction of mfERG high-frequency components. The mfERG low-frequency components were slightly larger than normal. None of the full-field flash ERG amplitudes (a-wave, b-wave, oscillatory potentials, or PhNR) was significantly different from normal. There were no consistent abnormalities found in the results of any blood test. Histologic findings included axonal loss and gliosis limited to the temporal optic nerve, reduction of nuclei within the retinal ganglion cell layer, and thinning of the temporal retinal RNFL. CONCLUSIONS. The existence of BOA in nonhuman primates warrants caution on the part of investigators who use these animals in experimental models of ophthalmic disease. (Invest Ophthalmol Vis Sci. 2005;46:3943‐3956) DOI:10.1167/iovs.041160 T he purpose of this article is to report the existence of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys (Macaca mulatta) and to characterize the structural and functional consequences of the condition. Initially, this form of optic atrophy was an incidental finding in a single animal, but further investigation and careful evaluation has demonstrated a significant prevalence of BOA among nonhuman primate from several different sources. Thus, BOA should be investigated and characterized so that it can be readily identified in primates that are used in vision research. Identification of BOA is important, not least because it may confound interpretation of scientific results. An extensive search of the National Library of Medicine database (PubMed; National Institutes of Health, Bethesda, MD), using keywords such as optic neuropathy, optic atrophy, optic nerve, monkey, and rhesus macaque, suggests that this entity has never before been described. METHODS Animals All experimental methods and animal care procedures adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and were approved by the local Institutional Animal Care and Use Committee (IACUC). In total, data for 38 adult rhesus monkeys (Macaca mulatta) are presented in this study. Nine animals were found to have BOA; their demographic data are presented in Table 1. Six of these were isolated from a population at one of our laboratories (Discoveries in Sight, Devers Eye Institute) after the initial subject was identified and confirmed by histopathology (BOA4). The other three monkeys with BOA were identified from a separate cohort located at the LSU Eye Center. Data for 29 other animals were used as the control. The control population consisted of normal healthy adults with an age range of 4 to 19 years. The control data were collected over the course of several years at Discoveries in Sight as a part of other IACUCapproved protocols. Intraocular pressure (IOP) was measured with a handheld tonometer (Tonopen; Oculab, Inc., Glendale, CA) with monkeys under ketamine or isoflurane anesthesia. The average of three readings each on two separate days is recorded in Table 1. Anesthesia