New research suggests that senolytic drugs, which remove harmful senescent cells that accumulate during aging, may be an effective therapy for glaucoma, a common age-related condition that leads to loss of vision.
In the short term, inflammation serves a useful purpose, as it helps to spur the repair and regeneration of tissue and rallies the immune system to defend against marauding invaders.
However, the chronic, smoldering, low-grade inflammation that occurs during aging can be incredibly harmful. The sources of this “inflammaging,” as some researchers describe it, include (but are not limited to) dysfunctional immune cells, cell debris, disruption to the gut microbiome, and senescent cells. Today, we are concerned about the latter after the release of a new study focusing on senescent cells and glaucoma [1].
The presence of senescent cells has been linked with a wide, and growing, range of age-related diseases due to their contribution to the elevated levels of systemic inflammation typically observed in older people. Senescent cells secrete a variety of pro-inflammatory signals that, collectively, are known as the senescence‐associated secretory phenotype (SASP).
Glaucoma is the loss of vision caused by the damage and degeneration to the retinal ganglion cells and the optic nerve. In the majority of cases, glaucoma is driven by increased pressure in the eye, which is caused by high blood pressure (hypertension) and damage to the tiny fluid channels in the eye that facilitate drainage.
The researchers here demonstrate that removing senescent cells with the senolytic drug dasatinib reduces ganglion cell death by half in an animal model of glaucoma.
Experimental ocular hypertension induces senescence of retinal ganglion cells (RGCs) that mimics events occurring in human glaucoma. Senescence‐related chromatin remodeling leads to profound transcriptional changes including the upregulation of a subset of genes that encode multiple proteins collectively referred to as the senescence‐associated secretory phenotype (SASP). Emerging evidence suggests that the presence of these proinflammatory and matrix‐degrading molecules has deleterious effects in a variety of tissues. In the current study, we demonstrated in a transgenic mouse model that early removal of senescent cells induced upon elevated intraocular pressure (IOP) protects unaffected RGCs from senescence and apoptosis. Visual evoked potential (VEP) analysis demonstrated that remaining RGCs are functional and that the treatment protected visual functions. Finally, removal of endogenous senescent retinal cells after IOP elevation by a treatment with senolytic drug dasatinib prevented loss of retinal functions and cellular structure. Senolytic drugs may have the potential to mitigate the deleterious impact of elevated IOP on RGC survival in glaucoma and other optic neuropathies.
Conclusion
Glaucoma currently has very limited treatment options, and this study offers a ray of hope for sufferers of the condition. This is the first time that senolytics have been shown to benefit mouse models of glaucoma, and the results are indeed promising. If these results can be translated to human trials, it is plausible that this condition could finally have a robust treatment option that protects patients from losing their sight.
As funding for senolytic research floods into the field, thanks to the increasing amount of interest in doing something about aging, we are likely to see more and more of these kinds of studies and, without a doubt, the list of diseases in which senescent cells have been shown to play a role will continue to grow.
Literature
[1] Rocha, L. R., Huu, V. A. N., La Torre, C. P., Xu, Q., Jabari, M., Krawczyk, M., … & Skowronska‐Krawczyk, D. (2019). Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension. Aging Cell.
