Rhesus macaques with an <i>OPA1</i> mutation demonstrate features of autosomal dominant optic atrophy
heterozygotes was demonstrated with pattern electroretinography. Histopathological analysis and immunohistochemical staining of postmortem retinal tissue suggested RGC loss in the papillomacular bundle, with reduced OPA1 and mitochondria in the RGC axons, indicating dysfunctional mitochondrial dynamics and reduced function consistent with ADOA. Ultrastructural changes were evident with TEM including dysmorphic mitochondria, axonal loss, myelin disruption, and hypertrophic astrocytic processes. The observed similar pattern of RGC loss and dysfunction coupled with phenotypic heterogeneity in our NHP model reflects the clinical variability observed in human ADOA patients indicating that therapeutic interventions in this foveate model will likely translate to the human condition.
Authors
- Sara M. Thomasy (ORCID: https://orcid.org/0000-0001-5617-9677)
- Nicholas Marsh‐Armstrong (ORCID: https://orcid.org/0000-0002-7843-6651)
- Marguerite F. Knipe (ORCID: https://orcid.org/0000-0003-3749-6495)
- Brad A. Fortune (ORCID: https://orcid.org/0000-0003-0284-5173)
- Sangwan Park (ORCID: https://orcid.org/0000-0003-0381-0386)
- S M Kim
- Leandro B. C. Teixeira (ORCID: https://orcid.org/0000-0001-9960-678X)
- Brian C. Leonard (ORCID: https://orcid.org/0000-0003-2080-8480)
- J. Timothy Stout
- Eliza Bliss‐Moreau (ORCID: https://orcid.org/0000-0002-0740-5612)
- Ala Moshiri (ORCID: https://orcid.org/0000-0002-4277-8094)
- Brett D. Story (ORCID: https://orcid.org/0000-0002-9771-9294)
- Nayeli Echeverria
- Lucy G Moore
- Jeffrey Rogers (ORCID: https://orcid.org/0000-0002-7374-6490)
- M. Isabel Casanova (ORCID: https://orcid.org/0000-0003-2337-5051)
- Sophie M. Le
- Monica Ardon
- Rui Chen (ORCID: https://orcid.org/0000-0002-4341-2908)
- Paige M. Karpinen
- Yi-Xiang Wang (ORCID: https://orcid.org/0000-0002-4021-4228)
- Laura J. Young
- Tracy N. Jaggers (ORCID: https://orcid.org/0000-0002-8842-2675)
- Ana C. Raposo
- Jaeho Shim (ORCID: https://orcid.org/0000-0002-2179-8950)
- Karolina P. Roszak
- Vanessa Ureno
- Ana Ripolles-Garcia
Institutions
- University of Wisconsin–Madison (US)
- Legacy Health (US)
- Baylor College of Medicine (US)
- Baylor Genetics (US)
- University of California, Davis (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-04-15
- DOI
- https://doi.org/10.1073/pnas.2509165123
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Institute on Aging
- National Institute of Mental Health
- National Eye Institute
- National Institute of General Medical Sciences