Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review.

Area of Science:

• Mitochondrial biology
• Ophthalmology
• Genetics

Background:

• Mitochondria are crucial for ATP production and metabolic regulation, particularly in energy-demanding ocular tissues.
• Mitochondrial dysfunction, including pathogenic mitochondrial DNA (mtDNA) variants, impairs ATP synthesis, induces oxidative stress, and can cause cell death.
• Ocular tissues like the retina, optic nerve, and retinal pigment epithelium rely heavily on mitochondrial function.

Purpose of the Study:

• To compile and review pathogenic variants in mtDNA associated with ophthalmic diseases.
• To highlight genetic variants, their pathogenic roles, and phenotypic consequences in ocular tissues.
• To discuss the role of mtDNA variants in both primary mitochondrial eye diseases and complex multifactorial conditions.

Main Methods:

• Literature review and compilation of existing research.
• Analysis of genetic variants and their association with ophthalmic phenotypes.
• Synthesis of information on pathogenic mechanisms and clinical significance.

Main Results:

• Identified numerous pathogenic mtDNA variants linked to Leber's hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, and other mitochondrial disorders.
• Detailed the pathogenic roles and phenotypic outcomes of these variants in ocular tissues.
• Presented emerging evidence for mtDNA variants in multifactorial eye diseases like glaucoma and AMD.

Conclusions:

• Mitochondrial DNA pathogenic variants are significant contributors to a spectrum of eye diseases.
• Understanding these variants is crucial for diagnosing and managing mitochondrial-related ophthalmic conditions.
• Further research into mtDNA's role in complex eye diseases is warranted.