The Present and Future of Mitochondrial-Based Therapeutics for Eye Disease

Mitochondrial dysfunction within the eye contributes to primarily mitochondrial diseases affecting the visual system such as Leber hereditary optic neuropathy (LHON) as well as more common ocular diseases, including glaucoma, diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration (AMD). For these reasons, druggable targets and gene therapies for improving mitochondrial function have been of significant interest within scientific and pharmaceutical endeavors seeking to improve visual outcomes in ocular disease. These therapies modulate mitochondrial functions, including mitochondrial membrane potential and membrane stability, redox signaling and oxidative stress, mitochondrial quality control including fusion/fission and biogenesis/mitophagy, apoptosis, and mitochondrial genetic-based therapies. As of now, several mitochondrial-targeted therapies have been approved in a limited number of countries, including photobiomodulation for AMD, idebenone for LHON, and SkQ1 for dry eye disease. Elamipretide for nonexudative AMD and gene therapy with GS010 for LHON have additionally shown encouraging results within clinical trials. Translational Relevance: Mitochondria are viable therapeutic targets for a broad spectrum of ocular diseases.