Abstract

SO.15.02

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

Kernt M., Neubauer A., Yu A., Kampik A., Welge-Lüßen U.
Augenklinik der LMU München

Objective: 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. Oxid. stress and elevated levels of TGF-beta play an important role in the pathogenesis of this neurodegenerative disease. Minocycline (M) was recently found to be neuroprotective in models of neuronal injury. This study investigates possible anti-apoptotic and cytoprotective effects of M on TMC and ONHA under cond. of oxid. stress and TGF-beta.
Methods: TMC and ONHA were treated with concentrations of M between 1µM and 150µM. Possible toxic effects and IC50 were evaluated after 24 hours by measuring the inhibition of cell proliferation (MTT). To investigate possible cytoprot. and anti-apopt. 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 24 hours after treatment with M alone, additional incubation with TGF-beta-2 and under conditions of oxid. stress.
Results: M concentrations from 1µM to 75µM showed no toxic effects in MTT assay neither on TMC nor on ONHA. Under conditions of oxid. stress both TMC and ONHA showed 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 alone, under cond. of oxid. stress and when additionally incubated with TGF-beta2.
Conclusions: We could show that M does not have toxic effects on TMC and ONHA cells in concentrations of up to 75µM. The observed increase in viability and ability to proliferate under oxid. stress 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 one protective pathway for TMC and ONHA to avoid progression of glaucomatous degeneration.

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