Rhesus macaques found to carry mutation that mirrors human hereditary blindness disorder, study finds

Researchers at the University of California, Davis (UC Davis) have identified a naturally occurring OPA1 mutation in rhesus macaques that closely mirrors autosomal dominant optic atrophy (ADOA), a progressive inherited eye disease in humans that affects vision and can lead to blindness.

The findings, published in Proceedings of the National Academy of Sciences, revealed that rhesus macaques carrying the mutation developed retinal and optic nerve abnormalities comparable to those observed in people with ADOA. The study could provide a valuable model for studying the disease and lead to new treatment options in humans, the researchers said.^1,2

“This model can serve as a valuable tool for further understanding the mechanisms underlying ADOA, developing novel diagnostic tools for this condition, and exploring potential therapeutic interventions,” they wrote.¹

ADOA is an inherited optic neuropathy that affects approximately 3 in 100,000 people worldwide and causes progressive bilateral vision loss.¹ Many patients are diagnosed between the ages of 10 and 30. The condition is most commonly associated with mutations in the OPA1 gene, which plays a critical role in mitochondrial fusion and cellular energy production. Mutations in OPA1 are associated with 65% to 90% of ADOA cases.¹

Although several investigational therapies are being explored in people, including idebenone and gene-targeted approaches, there are currently no established treatments for ADOA in either human or veterinary patients.^1,2

Macaques developed changes similar to human disease

The mutation was identified in a rhesus macaque colony at the California National Primate Research Center at UC Davis. Researchers evaluated 50 heterozygous macaques, 2 homozygotes, and 8 wild-type controls.¹

Affected macaques developed retinal and optic nerve abnormalities that closely resembled those reported in humans with ADOA, including bilateral optic nerve pallor, thinning of the retinal nerve fiber layer, retinal ganglion cell loss, and peripapillary retinal thinning detected on optical coherence tomography.¹

The animals also demonstrated reduced electroretinography responses consistent with retinal dysfunction. Histopathology findings included retinal thinning, myelin disruption, and hypertrophic astrocytic changes. Ultrastructural analysis additionally identified abnormal mitochondrial morphology within affected retinal cells.¹

Why rodents fall short, and macaques don't

Most research on inherited optic neuropathies has relied on rodent models, which produce a milder phenotype that does not fully replicate the human condition. Rhesus macaques, however, share a highly similar retinal architecture with humans, including a fovea—the specialized area responsible for sharp central vision—making them a more clinically relevant platform for studying disease progression and testing interventions.¹

The researchers said the study could help gene therapy approaches for ADOA, including gene augmentation and mRNA strategies currently being developed, before they advance to human clinical trials.¹

A behavioral study that took on a different turn

The discovery began with a then-veterinary student and a research plan that never came to be. First author Tracy Jaggers, DVM, then enrolled at Western University College of Veterinary Medicine, had originally planned a behavioral study at the UC Davis primate center.

When COVID-19 pandemic restrictions prevented her from traveling to the facility, Jaggers and senior author Sara Thomasy, DVM, PhD, DACVO, were left with an existing dataset of macaques carrying an uncharacterized OPA1 mutation, which had been identified by sequencing the DNA of 1800 animals at the center in collaboration with Baylor College of Medicine. According to UC Davis, the mutation in the data had never been tied to eye disease.²

"It didn't look very obvious to me that there's something going on. I actually expected it to be a negative study," Thomasy, a professor of comparative ophthalmology with dual appointments at the Weill School of Veterinary Medicine and the Department of Ophthalmology and Vision Science at UC Davis, said.² "But Tracy was so tenacious with the data."

That tenacity paid off. Using imaging techniques adapted from human ophthalmology, Jaggers and Thomasy identified a macaque with eye abnormalities that also carried a single copy of the OPA1 mutation, a discovery that led to National Eye Institute funding to expand the work. The grant now allows researchers to follow how the disease develops over time and compare outcomes in animals with one versus two copies of the mutation.

According to UC Davis, Thomasy and other colleagues at the UC Davis Health Department of Ophthalmology and Vision Science have also identified several other eye diseases in macaques that are equivalent to inherited human eye diseases. These include achromatopsia, which affects cone cells responsible for color vision, and age-related macular degeneration.²

References

1. Jaggers TN, Ripolles-Garcia A, Moshiri A, et al. Rhesus macaques with an OPA1 mutation demonstrate features of autosomal dominant optic atrophy. Proc Natl Acad Sci USA. 2026;123(16):e2509165123. doi:10.1073/pnas.2509165123
2. Fell A. Identifying genetic causes of blindness in people and macaques. UC Davis News. April 28, 2026. Accessed May 21, 2026. https://www.ucdavis.edu/news/identifying-genetic-causes-blindness-people-and-macaques