摘要：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.
其他摘要：Abstract 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.
