Macaque model of inherited macular dystrophy

Abstract

Inherited macular dystrophies are a group of genetic disorders resulting in progressive damage to the cells in the macula, leading to vision loss. Although gene- and cell-based therapies offer promising approaches for these conditions, progress is hindered by the lack of animal models that recapitulate the macular changes observed in patients. In JCI insight, Xialin Liu’s team reports the first spontaneous nonhuman primate model of inherited macular dystrophy. Few years ago, while performing ocular biometric measurements in a cohort of Macaca fascicularis using advanced imaging techniques, the team identified a 6.8-year-old male with macular abnormalities. Whole-genome sequencing data revealed that the animal was carrying a BEST1p.Q327E variant. In humans, mutations in the BEST1 gene give rise to Best vitelliform macular dystrophy (BVMD), one of the most common inherited macular dystrophies. Longitudinal imaging of the animal over two years revealed progressive macular changes, lipid-rich deposit accumulation, retinal pigment epithelium disruption and photoreceptor degeneration, recapitulating early human BVMD pathology. Histological analysis also indicated a buildup of damaged cone mitochondria. The model, which provides new insights into the pathophysiological processes involved in macular diseases, could be valuable for testing potential therapies.

Original reference: Yi, W. et al. JCI Insight 10, e190807 (2025)