Oral 8-aminoguanine against age-related retinal degeneration.

Abhishek Vats, Yibo Xi, Amanda S Wolf-Johnston, Owen D Clinger, Riley K Arbuckle, Li Sheng, Xingcan Jiang, Chase D Dermond, Jonathan Li, Donna B Stolz, Anthony J St Leger, José-Alain Sahel, Edwin K Jackson, Lori A Birder, Yuanyuan Chen

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · pubmed

Paper

Abstract

Vision decline in the elderly, often due to retinal aging, predisposes individuals to pathologies like age-related macular degeneration. Currently, there are few effective oral treatments for this condition. Our study introduces an oral agent, 8-aminoguanine (8-AG), which targets age-related retinal degeneration using an aged Fischer 344 rat model. When administered in drinking water at a low dose for 8 weeks starting at 22 months of age, 8-AG significantly preserves retinal structure and function, as evidenced by increased retinal thickness, enhanced photoreceptor integrity, and improved electroretinogram responses. 8-AG reduces apoptosis, oxidative damage, and microglial/macrophage activation in aging retinae. 8-AG also mitigates retinal inflammation at transcriptional and cytokine levels. Extending treatment to 17 weeks further amplifies these protective effects. Given its efficacy in various disease models, 8-AG shows great promise as an anti-aging compound with the potential to mitigate common hallmarks of aging.

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Research summary

Oral administration of 8-aminoguanine significantly preserves retinal structure and function in an aged rat model. The study addresses a potential therapeutic approach to mitigate age-related retinal degeneration, which is a direct concern of aging and its associated pathologies.

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