Mitochondrial Open Reading Frame of the 12S rRNA Type-c: Potential Therapeutic Candidate in Retinal Diseases.

Antioxidants (Basel, Switzerland)2023PMID: 36830076

View on PubMed DOI: 10.3390/antiox12020518

Plain Language Summary

Review examining MOTS-c as a therapeutic candidate in retinal diseases—particularly age-related macular degeneration and diabetic retinopathy—covering its protective effects on retinal pigment epithelial cells under oxidative and mitochondrial stress, its anti-senescence properties, and its potential for intravitreal or systemic delivery to protect photoreceptors and RPE cells from mitochondria-driven degeneration. Establishes the rationale for MOTS-c in ophthalmology. Provides the first systematic examination of MOTS-c's therapeutic potential in retinal diseases—where RPE and photoreceptor mitochondrial dysfunction drives irreversible vision loss, positioning mitochondrial peptide supplementation as a novel approach to preventing blindness in AMD and diabetic retinopathy.

Abstract

Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is the most unearthed peptide encoded by mitochondrial DNA (mtDNA). It is an important regulator of the nuclear genome during times of stress because it promotes an adaptive stress response to maintain cellular homeostasis. Identifying MOTS-c specific binding partners may aid in deciphering the complex web of mitochondrial and nuclear-encoded signals. Mitochondrial damage and dysfunction have been linked to aging and the accelerated cell death associated with many types of retinal degenerations. Furthermore, research on MOTS-c ability to revive oxidatively stressed RPE cells has revealed a significant protective role for the molecule. Evidence suggests that senescent cells play a role in the development of age-related retinal disorders. This review examines the links between MOTS-c, mitochondria, and age-related diseases of the retina. Moreover, the untapped potential of MOTS-c as a treatment for glaucoma, diabetic retinopathy, and age-related macular degeneration is reviewed.

Authors

Mohtashami, Zahra; Singh, Mithalesh Kumar; Neto, Farid Thomaz; Salimiaghdam, Nasim; Hasanpour, Hossein; Kenney, M Cristina

Keywords

MOTS-cage-related macular degenerationdiabetic retinopathyglaucomamitochondrial dysfunction