While age-related macular degeneration (AMD) development is linked to a combination of genetic and environmental factors, the mechanism of the disease begins with changes in the retinal pigment epithelium (RPE) function that, researchers say, is associated with oxidative stress. A review published in Survey of Ophthalmology examines current research on cytoprotective oxidative stress pathways and antioxidant therapy at various stages of macular degeneration.

The review affirms the role of oxidative stress in the pathophysiology of AMD and identifies key protective transcription factors that play a role in cytoprotective pathways.  “Aging can reduce the body’s adaptation to stress. The accumulated insults from genetic and environmental factors impair cytoprotective pathways that result in cellular dysfunction. If this impairment sufficiently damages tissue, aging transitions into disease,” the study explains.

The research review shows the effects of oxidative stress on both the mitochondria and autophagy. Mitochondria of RPE cells play a vital role in RPE cell function. When mitochondria are damaged by oxidative stress, the process of mitophagy (that is, the removal of damaged mitochondrial cells) may be compromised, which can lead to widespread cellular death and dysfunction. Meanwhile, oxidative stress, according to the study, is also linked to autophagy failure, which leads to the accumulation of dead RPE cells and contributes to AMD progression.


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Current research also links oxidative stress with the activation of the neuroprotective immune response which, researchers suspect, may later convert to pathological inflammation and shows a significant association between genetic variants encoding proteins related to oxidative stress and response to AMD.

The review also covers various accepted and rejected supported management strategies for AMD. A diet in antioxidant-rich fruits and vegetables, cigarette cessation, regular exercise, and antioxidant therapy can all mitigate the risk of AMD, the review shows. No evidence supports caffeine consumption as a risk factor for AMD. Likewise, no evidence supports intermittent fasting or calorie restrictions as a way to treat AMD.

Agents shown, through in vivo modeling, to have an antioxidative effect include lutein, zeaxanthin, meso-zeaxanthin, eicosapentaenoic, docosahexaenoic acid, curcumin, fucoidan, flavonoids, quercetin, cerium oxide nanoparticles, and coenzyme Q10. 

The investigators look forward to building on the understanding of the role of oxidative stress among the multifactorial etiologies in AMD, with the hopes that it could bolster promising treatments using antioxidants and systems that deliver molecules to specific cell types and their subcellular structures.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Jabbehdari S, Handa JT. Oxidative stress as a therapeutic target for the prevention and treatment of early age-related macular degeneration. Surv Ophthalmol. Published online September 19, 2020. doi: 10.1016/j.survophthal.2020.09.002.