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

Experimental ocular hypertension (IOP) induces senescence of retinal ganglion cells (RGCs) that mimicks events occurring in human glaucoma. An established transgenic p16-3MR mouse model in which the systemic administration of the small molecule ganciclovir (GCV) selectively kills p16INK4a-expressing cells was used to compare transcriptomes of retinas from IOP and control eyes in GCV-treated and non-treated mice, to investigate how experimental removal of senescent p16INK4a-positive cells impacts retinal cells in conditions resembling glaucoma. Overall design: All six mice carried the p16-3MR transgene. High IOP was induced in one eye of each of the 6 mice and the other was a normal IOP controls. Three mice were subsequently (the same day) treated with GCV and the other three were mock treated. GCV injections were repeated daily for a total of three days, at which point the mice were sacrified, retinas were dissected and total RNA was isolated for transcriptomic analyses.