Characterization of Unique Bilateral Optic Atrophy in a Cynomolgus Macaque

Abstract

Purpose : Cynomolgus macaques are used commonly in preclinical toxicology research because of their homology to human anatomy, particularly ocular anatomy. Bilateral optic atrophy affecting the temporal optic nerve has been infrequently reported in cynomolgus and rhesus macaques. Further characterization will improve understanding of this naturally occurring phenotype in an important preclinical model.

Methods : A drug naïve three-year-old, spontaneously blind, female cynomolgus macaque underwent physical and ophthalmic examination, fundus photography, electroretinogram (ERG), optical coherence tomography (OCT), magnetic resonance imaging (MRI), and histology were performed.

Results : The animal was determined to be behaviorally blind by lack of visual tracking and absence of response to visual stimuli. Ophthalmic exam showed both optic discs were markedly depressed, degenerate, and atrophic. Intraocular pressures were normal. No significant changes were noted on MRI and optic nerves were symmetric; however, size of the optic nerve on MRI was not compared to a clinically normal animal. Retinal function was within expected limits as assessed by ISCEV standard ERG, but visual evoked potential (VEP) was undetectable, indicating dysfunction of the optic nerve and/or central visual pathways (Figure 1). Microcystoid macular degeneration and decreased nerve fiber and retinal ganglion cell (RGC) layers was prominent on OCT and histological sections (Figure 2). Microscopically, severe optic nerve atrophy was noted along with marked loss of RGCs in the presence of normal outer retinal layers.

Conclusions : Bilateral optic atrophy with severe degeneration of the optic nerve was confirmed by ophthalmic exam and histology, with functional loss of vision related to undetectable flash VEP, and microcystoid macular degeneration which was different from previous reports. Genomic analysis is pending. Bilateral optic atrophy is a rare occurrence in cynomolgus monkeys, but has potentially serious consequences for vision and careful ophthalmologic pre-screening should be completed prior to inclusion in ocular studies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1: Loss of visual evoked potential (VEP) bilaterally

 

Figure 2: Representative OCT image showing microcystoid macular degeneration which was apparent bilaterally.