Evaluating the neuroprotective impact of senolytic drugs on human vision.
Evaluating the neuroprotective impact of senolytic drugs on human vision.
复制标题
评估衰老清除药物对人类视力的神经保护作用。
DOI：
10.1038/s41598-020-78802-4
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发表时间：
2020-12-10
影响因子：
4.6
通讯作者：
Baxter SL
中科院分区：
文献类型：
--
作者：
El-Nimri NW;Moore SM;Zangwill LM;Proudfoot JA;Weinreb RN;Skowronska-Krawczyk D;Baxter SL
青光眼是视网膜神经节细胞（RGCs）的慢性神经退行性疾病，是全球范围内不可逆失明的主要原因。其管理目前侧重于降低眼内压以减缓疾病进展。然而，青光眼的疾病改善、神经保护治疗仍然是一个主要的未满足的需求。最近，在青光眼患者的眼睛中观察到了衰老细胞，这为青光眼的替代疗法提供了一个潜在的途径。先前的研究表明，靶向衰老的RGC以去除（即，衰老清除方法）在小鼠高眼压模型中保护了健康的RGC并保留了视觉功能。然而，衰老清除药物对人类患者视力的影响尚不清楚。在这里，我们使用现有的临床数据进行了回顾性队列研究，在28人青光眼患者谁曾暴露于senolytics。老年痴呆暴露与视力下降、眼内压升高或治疗眼科医生记录的老年痴呆相关不良眼部反应无关。此外，暴露于senolytics的患者（n = 9）与未暴露于senolytics的匹配青光眼患者（n = 26）相比，未表现出更快的青光眼性视野损伤进展。这些结果表明，senolytic药物不携带显着的眼毒性，并提供了进一步的支持，额外的评估潜在的神经保护作用的senolytic青光眼和其他神经退行性疾病。
Glaucoma, a chronic neurodegenerative disease of retinal ganglion cells (RGCs), is a leading cause of irreversible blindness worldwide. Its management currently focuses on lowering intraocular pressure to slow disease progression. However, disease-modifying, neuroprotective treatments for glaucoma remain a major unmet need. Recently, senescent cells have been observed in glaucomatous eyes, exposing a potential pathway for alternative glaucoma therapies. Prior studies demonstrated that targeting senescent RGCs for removal (i.e., a senolytic approach) protected healthy RGCs and preserved visual function in a mouse ocular hypertension model. However, the effects of senolytic drugs on vision in human patients are unknown. Here, we used existing clinical data to conduct a retrospective cohort study in 28 human glaucoma patients who had been exposed to senolytics. Senolytic exposure was not associated with decreased visual acuity, elevated intraocular pressure, or documentation of senolytic-related adverse ocular effects by treating ophthalmologists. Additionally, patients exposed to senolytics (n = 9) did not exhibit faster progression of glaucomatous visual field damage compared to matched glaucoma patients (n = 26) without senolytic exposure. These results suggest that senolytic drugs do not carry significant ocular toxicity and provide further support for additional evaluation of the potential neuroprotective effects of senolytics on glaucoma and other neurodegenerative diseases.
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影响因子：
--
作者：
LESKE, MC;CONNELL, AMS;HYMAN, L
通讯作者：
HYMAN, L
影响因子：
16.6
作者：
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通讯作者：
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影响因子：
11.1
作者：
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通讯作者：
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影响因子：
18.2
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通讯作者：
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影响因子：
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通讯作者：
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