Fig. 5: A genetic rhesus macaque model of human optic atrophy.

Rhesus macaques heterozygous for an optic atrophy 1 (OPA1) mutation exhibit structural and functional changes consistent with retinal ganglion cell (RGC) loss. The horizontal ovoid, light pink optic nerve head of a normal 24-year-old female rhesus macaque wildtype for the OPA1 mutation (a) differs from the markedly smaller, atrophic optic nerve head of a 28-year-old female heterozygous for an OPA1 mutation (b); the OPA1 heterozygote did have moderate cataract which limited the quality of the fundus photography. Automated peripapillary optic nerve head scans of the normal control (wildtype: WT) (c and e) demonstrate normal retinal nerve fiber layer (RNFL) thickness in all regions while the OPA1 heterozygote (HET) (d and f) demonstrates a markedly reduced RNFL thickness in essentially all regions. TMP (T): Temporal, SUP (S): Superior, NAS (N): Nasal, INF (I): Inferior, ST: Superotemporal, IT: Inferotemporal, SN: Superonasal, IN: Inferonasal, and OS: left eye. Manual RNFL measurements of the two rhesus macaques (g) confirmed the findings in the automated scans. Manual RNFL measurements were compared between 8 OPA1 heterozygotes and 8 age-, sex-matched wild type controls (Supplementary Data 7) using a two-way analysis of variance (ANOVA) and Sidak’s multiple comparison test. Peripapillary RNFL was significantly decreased (*P = 0.03) in the superotemporal region in 8 OPA1 heterozygotes versus 8 age-, sex-matched controls (h). Data represent mean values ± standard deviation. Source data are provided in the Source Data file.