Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension

Experimental ocular hypertension induces senescence of retinal ganglion
cells (RGCs) that mimicks 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 senescenceassociated
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.