Treatment of age-related visual impairment with a mitochondrial-acting peptide.

Abstract

Age-related visual decline and disease due to neural dysfunction are major sources of disability that have resisted effective treatment. In light of evidence that visual impairment and mitochondrial dysfunction advance with age, we characterized age-related decline of spatial visual function in mice and investigated whether treating aged mice with a drug, Elamipretide (SS31), that has been reported to improve mitochondrial function would treat it. Impaired photopic acuity measured with a virtual optokinetic system emerged near 18 months, and declined to ∼40% below normal by 34 months. Daily application of the synthetic peptide Elamipretide, which has high selectivity for mitochondrial membranes that contain cardiolipin, and promotes efficient electron transfer, was able to mitigate visual decline from 18 months. Daily application from 24 months, when acuity was reduced by ∼16%, reversed visual decline and normalized function within 2 months; recovered function that persisted for at least 3 months after treatment was withdrawn. A single treatment at 24 months also delayed subsequent visual decline. Daily application from 32 months took longer to affect change, but enabled substantial improvement within 2 months. The effects of age and Elamipretide treatment on contrast sensitivity were similar to those on acuity, systemic and eye drop applications of Elamipretide had comparable effects, scotopic spatial visual function was largely unaffected by age or treatment, and altered function was independent of variation in optical clarity. These data indicate that Elamipretide treatment adaptively alters the aging visual system, and provide a rationale to investigate whether mitochondrial dysfunction is a treatable pathophysiology of human visual aging and age-related visual disease.