Evaluating the neuroprotective impact of senolytic drugs on human vision
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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.
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In a retrospective study of 28 patients with glaucoma, senolytic exposure did not affect visual acuity or intraocular pressure, and did not have toxic effects.
“Although a study in a mouse model showed that dasatinib prevented glaucoma-dependent loss of retinal functions and cellular structure, 41 a retrospective study assessing the effects of senolytic drugs on vision in 28 patients with glaucoma showed that senolytic exposure did not affect visual acuity or intraocular pressure, and did not have toxic effects.74”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [74]
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- Authors
- El-Nimri, N. W., Moore, S. M., Zangwill, L. M., Proudfoot, J. A., Weinreb, R. N., Skowronska-Krawczyk, D., & Baxter, S. L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Baxter, Sally L.
- Venue
- Scientific Reports
- Published
- 2020-12-10
- Volume
- 10
- Issue
- 1
- Pages
- 21752-21752
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7730173
- OpenAlex
- W3111262807
- Cited by
- 22
- References
- 35
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 11 · 2021: 1 · 2020: 1
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (P30EY022589, EY027011, T15LM011271)
- RBP award
- Glaucoma Research Foundation Shaffer Award
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- senolytics, glaucoma, retinal ganglion cells, neuroprotection, senescent cells, visual acuity, intraocular pressure, visual field damage, ocular toxicity, disease-modifying therapy, neurodegenerative diseases
- MeSH terms
- Imatinib Mesylate, Dasatinib, Adult, Aged, Aged, 80 and over, Animals, Disease Models, Animal, Female, Glaucoma, Humans, Intraocular Pressure, Male, Middle Aged, Retinal Ganglion Cells, Retrospective Studies, Vision, Ocular, Visual Acuity, Cohort Studies, Mice, Antibodies, Monoclonal, Humanized
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