Retinal Nerve Fiber Layer Thickness in Normal Rhesus Macques and in Animals with a Polymorphism in OPA1

Abstract

Purpose : We measured the thickness of the circumpapillary retinal nerve fiber layer (RNFL) in normal rhesus macaques (Macaca mulatta) and also in animals with a single nucleotide polymorphism (SNP) in the OPA1 gene predicted to be pathologic. We hypothesized a decreased RNFL thickness in OPA1 mutants compared to normal counterparts. There is no treatment for Dominant Optic Atrophy (DOA) associated with mutations in OPA1 and a large animal disease model could accelerate clinical trials.

Methods : Seven primates with a SNP in the OPA1 gene and 51 wild type animals underwent ophthalmic exams that included a circumpapillary OCT scan of the RNFL. Electroretinography (ERG) was performed, including photopic negative response (PhNR) to assess retinal ganglion cell (RGC) function. Results of the RNFL scans were analyzed using a two-way ANOVA and Sidak’s multiple comparison test. The PhNR results were analyzed with a Mann-Whitney non-parametric test.

Results : Female NHPs have thicker RNFL than males in the inferotemporal region at location 270 Degrees (P=0.039). There was no significant difference in the RNFL thickness between the OPA1and wildtype groups at any location. However, when OPA1 animals were compared to age-and sex-matched individuals (Fig 1), two of the oldest OPA1 animals had RNFL thinning in the temporal and nasal regions. OPA1 animals as a group had reduced RGC function (Fig 2) as measured by PhNR at 72 ms (P=0.0121) and at the PhNR minimum (P=0.0098).

Conclusions : The RNFL of rhesus monkeys shows significant regional differences between sexes, as seen in humans. There were no RNFL differences between OPA1 animals and controls. However, when comparing the individual OPA1 mutants to age- and sex-matched wildtype counterparts, there was RNFL thinning in older OPA1 individuals. OPA1 animals had reduced RGC function when compared to wild type controls suggesting reduced function at all ages. Since DOA can have a relatively late onset of disease, it is possible animals with this OPA1 polymorphism represent an NHP model of hereditary optic neuropathy.

This is a 2021 ARVO Annual Meeting abstract.

 

Figure 1 Older OPA1 animals have a thinner RNFL than age-matched counterparts in the temporal and nasal regions.

 

Figure 2. Photopic Negative Response is reduced in the OPA1 (gray) group compared to controls (black) at both 72mS and at the minimum.