Abstract

Glaucoma is a heterogeneous eye disease causing atrophy of the optic nerve head (ONH). The optic nerve is formed by the axons of the retinal ganglion cells (RGCs) that transmit visual input to the brain. The progressive RGC loss during glaucoma leads to irreversible vision loss. An elevated intraocular pressure (IOP) is described as main risk factor in glaucoma. In this study, a multielectrode array (MEA)-based ex vivo glaucoma acute model was established and the effects of hydrostatic pressure (10, 30, 60, and 90 mmHg) on the functionality and survival of adult male and female wild-type mouse (C57BL/6) retinae were investigated. Spontaneous activity, response rate to electrical and light stimulation, and bursting behavior of RGCs was analyzed prior, during, and after pressure stress. No pressure related effects on spontaneous firing and on the response rate of the RGCs were observed. Even a high pressure level (90 mmHg for 2 h) did not disturb the RGC functionality. However, the cells’ bursting behavior significantly changed under 90 mmHg. The number of spikes in bursts doubled during pressure application and stayed on a high level after pressure stress. Addition of the amino sulfonic acid taurine (1 mM) showed a counteracting effect. OFF ganglion cells did not reveal an increase in bursts under pressure stress. Live/dead staining after pressure application showed no significant changes in RGC survival. The findings of our ex vivo model suggest that RGCs are tolerant toward high, short-time pressure stress.

Highlights

  • Glaucoma is the second leading cause of blindness worldwide (Quigley, 1996; Quigley and Broman, 2006; Tham et al, 2014)

  • In the control group without pressure lid, the mean firing frequency decreased by 23% from 11.36 ± 12.08 Hz to 8.76 ± 10.78 Hz and increased by 23% to 10.80 ± 11.78 Hz during the post-phase

  • The retinal ex vivo pressure model established here serves as a glaucoma acute model for short-time increased intraocular pressure (IOP)

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Summary

Introduction

Glaucoma is the second leading cause of blindness worldwide (Quigley, 1996; Quigley and Broman, 2006; Tham et al, 2014). The main risk factor in glaucoma is an increased intraocular pressure (IOP). IOP mainly depends on the production and outflow of aqueous humor. Aqueous humor is secreted by the epithelium of the ciliary body into the posterior chamber. It subsequently enters the anterior chamber via the Retinal Activity Under Hydrostatic Pressure pupil by moving down an osmotic gradient. Blockage of the outflow by ongoing humor production results in an increased IOP. Lowering the IOP by medical treatment in the form of eye drops, laser treatment or surgical treatment is considered the standard therapy

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