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口服8-氨基鸟嘌呤治疗年龄相关性视网膜变性。

Oral 8-aminoguanine against age-related retinal degeneration.

作者信息

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

机构信息

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

Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Commun Biol. 2025 May 26;8(1):812. doi: 10.1038/s42003-025-08242-1.

DOI:10.1038/s42003-025-08242-1
PMID:40419664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12106806/
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.

摘要

老年人视力下降通常是由于视网膜老化，这使个体易患年龄相关性黄斑变性等疾病。目前，针对这种情况的有效口服治疗方法很少。我们的研究引入了一种口服药物8-氨基鸟嘌呤（8-AG），它使用老年Fischer 344大鼠模型来针对年龄相关性视网膜变性。从22个月大开始，以低剂量在饮用水中给药8周，8-AG能显著保留视网膜结构和功能，视网膜厚度增加、光感受器完整性增强以及视网膜电图反应改善都证明了这一点。8-AG可减少衰老视网膜中的细胞凋亡、氧化损伤和小胶质细胞/巨噬细胞激活。8-AG还在转录和细胞因子水平减轻视网膜炎症。将治疗延长至17周可进一步增强这些保护作用。鉴于其在各种疾病模型中的疗效，8-AG作为一种具有减轻衰老常见特征潜力的抗衰老化合物显示出巨大前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/a9b5e1a04c42/42003_2025_8242_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/8e47a6584a5e/42003_2025_8242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/a663a8f9478f/42003_2025_8242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/1d6e19e58fff/42003_2025_8242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/59db4a0e10db/42003_2025_8242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/aed2d49addc4/42003_2025_8242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/bb438967c975/42003_2025_8242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/1cc5c1d395d9/42003_2025_8242_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/a9b5e1a04c42/42003_2025_8242_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/8e47a6584a5e/42003_2025_8242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/a663a8f9478f/42003_2025_8242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/1d6e19e58fff/42003_2025_8242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/59db4a0e10db/42003_2025_8242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/aed2d49addc4/42003_2025_8242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/bb438967c975/42003_2025_8242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/1cc5c1d395d9/42003_2025_8242_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b42/12106806/a9b5e1a04c42/42003_2025_8242_Fig8_HTML.jpg

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Age-Related Changes in the Glycolytic Enzymes of M2-Isoform of Pyruvate Kinase and Fructose-1,6-Bisphosphate Aldolase: Implications to Age-Related Macular Degeneration.年龄相关的 M2 型丙酮酸激酶同工酶和果糖-1,6-二磷酸醛缩酶糖酵解酶的变化：对年龄相关性黄斑变性的影响。
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