Cellular senescence in the glaucomatous outflow pathway

Abstract

The mechanisms responsible for the progressive malfunction of the trabecular meshwork (TM)-Schlemm's canal (SC) conventional outflow pathway tissue in primary open angle glaucoma (POAG) are still not fully understood. To determine whether POAG is characterized by an accumulation of senescent cells, similar to what has been described in other diseases, we have compared the levels of the senescence marker senescence-associated-β-galactosidase (SA-β-gal) in the outflow pathway cells of POAG and age-matched control donors. POAG donors demonstrated a statistically significant fourfold increase in the percentage of SA-β-gal positive cells. These results suggest a potential role for cellular senescence in the pathophysiology of the outflow pathway.

Impaired angiopoietin/Tie2 signaling compromises Schlemm’s canal integrity and induces glaucoma

“…In addition, considering that VEGFC-VEGFR3 signaling plays an essential role in SC formation (8,9) and that Angpt-Tie2 signaling shares this role, it is supposed that there is a close crosstalk between those signaling pathways in SC. Cellular senescence of SC is associated with accumulation of harmful stimuli and reactive oxygen species, which may cause dysfunctional drainage in humans and mice (39,54). Along with the previous report demonstrating decreased AHO and reduced expression of lymphatic markers such as Prox1 and VEGFR3 in aged SC (8), we reveal here that aged SC ECs exhibit attenuated intercellular junctions and decreased cellularity and transcytosis together with an attenuated Angpt-Tie2 system.…”

Lymphatic regulator PROX1 determines Schlemm’s canal integrity and identity

“…The senescence of SC in aged mice is quite similar to that in aged humans (46). However, there are only few works in the literature depicting the integrity of SC ECs, except decreased densities of transendothelial pores in SC ECs, depending on AHO with aging (56).…”

Functional analysis of differentially expressed genes associated with glaucoma from DNA microarray data

“…Because of its role in regulating energy metabolism and production, GAL may be used as a biomarker for monitoring or restoring the function of optical neural functions. CXCL6 is a cytokine that induces the directed migration of monocytes and neutrophils (Yoshie et al, 2001) and was found to be modulated in glaucoma (Liton et al, 2006;Lukas et al, 2008). Paylakhi et al (2011) further reported that CXCL6 was regulated by pituitary homeobox 2 in glaucoma.…”