Mitochondria dysfunction in disease
Mitochondria role in cell function
Mitochondria play a critical role in cellular health and function. Most well known as the “powerhouse of the cell”, mitochondria produce the vast majority of cellular energy in the form of ATP (adenosine triphosphate). Mitochondria have a number of other critical roles including signaling, mitophagy (mitochondrial repair) managing metabolic and oxidative stress response, biogenesis response to energy demands, spatial calcium buffering, and apoptosis (regulating orderly cell death).
Mitochondria role in vision
The visual systems ranks among the highest in the body for energy consumption. Photoreceptors convert light to neurochemical signals, a task that entails unusually high energy requirements, calcium ion transients, and oxidative stress. The visual system is particularly vulnerable to functional deficits induced by deficiencies in energy metabolism (1).
Mitochondrial dysfunction in retinal degeneration
Photoreceptor degeneration can result from any changes that alter energy metabolism, oxygen tension or ionic balance in the outer retina. Defects in the metabolic pathways that produce ATP underlie a number of retinal pathologies. Mitochondrial dysfunction is implicated in the underlying pathological basis for tissue damage in Retinitis Pigmentosa (2), Glaucoma (4), Dry AMD (3,4), and other retinal diseases.
Next Generation Mitochondrial Protective Approach
Library of Mitochondrial Protective Compounds
MitoChem has developed a new class of small molecules designed to treat neurodegeneration by protecting mitochondrial homeostasis (structure and function) from metabolic and oxidative stress caused by aging, genetic or environmental factors. The approach involves a unique mechanism of action and first in class target, with the potential to treat a broad range of neurodegenerative diseases. The compounds protect mitochondrial function, regardless of the underlying cause of stress or dysfunction. The lead compound, MC16, is optimized for ocular delivery. The first indication is retinitis pigmentosa, an orphan disease; the second indications are dry AMD and glaucoma.
References:
1. Wong-Riley, Energy metabolism of the visual system, Eye & Brain (2010) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515641/pdf/eb-2-099.pdf
2. Murakami et. al., Necrotic enlargement US National Library of Medicine, Neuropathy, ataxia, and retinitis pigmentosa, Cell Death Discovery (2015) https://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa#genes
3. Fisher CR, Ferrington DA. Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE. Invest Ophthalmol Vis Sci. 2018 Mar 20;59(4): AMD41-AMD47. doi: 10.1167/iovs.18-24289
4. Kamel K, Farrell M, O'Brien C. Mitochondrial dysfunction in ocular disease: Focus on glaucoma. Mitochondrion. 2017 Jul; 35:44-53. doi: 10.1016/j.mito.2017.05.004)