Minocycline is cytoprotective in human trabecular meshwork cells and optic nerve head astrocytes by increasing expression of XIAP, Survivin and Bcl‐2

Abstract

Abstract Purpose: Primary open‐angle glaucoma (POAG) is one of the leading cause for blindness. Activation of optic nerve head astrocytes (ONHA) and loss of trabecular meshwork cells (TMC) are pathognomonic for this disease. Oxidative stress (OS) and elevated levels of TGF‐beta play an important role in the pathogenesis of this neurodegenerative disease. This study investigates possible anti‐apoptotic and cytoprotective effects of Minocycline (M) on TMC and ONHA under OS and TGF‐beta. Methods: TMC and ONHA were treated with 1μM to 150μM M. Possible toxic effects and IC50 were evaluated after 24h (MTT). To investigate possible protective effects of M on TMC and ONHA, cell proliferation and viability was examined. Expression of XIAP, Survivin as well as Bcl‐2 and their mRNA was assessed by RT‐PCR 24h after treatment with M alone, additional incubation with TGF‐beta‐2 and OS. Results: M concentrations from 1μM to 75μM showed no toxic effects on TMC and ONHA. Under conditions of OS both TMC and ONHA showed an increase in viability and ability to proliferate when treated with 20‐40μM M. RT‐PCR yielded an overexpression of XIAP, Survivin and Bcl‐2, when TMC or ONHA cells were treated with 20‐40μM M for 24 hours, under OS and when additionally incubated with TGF‐beta2. Conclusions: We could show that M does not have toxic effects on TMC and ONHA cells up to 75μM. The observed increase in viability and proliferation under OS and TGF‐beta2 and the overexpression of XIAP, Survivin and Bcl‐2 after treatment with 20‐40μM M might prevent apoptotic‐cell‐death in response to cellular stress and may be a protective pathway for TMC and ONHA to avoid progression of glaucomatous degeneration.