Communications biology · 2025
Oral 8-aminoguanine against age-related retinal degeneration.
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Vats Abhishek, Xi Yibo, Wolf-Johnston Amanda S, Clinger Owen D, Arbuckle Riley K, Sheng Li, Jiang Xingcan, Dermond Chase D, Li Jonathan, Stolz Donna B, St Leger Anthony J, Sahel José-Alain, Jackson Edwin K, Birder Lori A, Chen Yuanyuan
Аннотация
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.