Glial Cell Activation and Oxidative Stress in Retinal Degeneration Induced by β-Alanine Caused Taurine Depletion and Light Exposure.

Ana Martínez-Vacas,Diego García-Ayuso,María Paz Villegas-Pérez,Francisco J Valiente-Soriano,Serge Picaud,Johnny Di Pierdomenico,Manuel Vidal-Sanz

doi:10.3390/ijms23010346

Abstract

We investigate glial cell activation and oxidative stress induced by taurine deficiency secondary to β-alanine administration and light exposure. Two months old Sprague-Dawley rats were divided into a control group and three experimental groups that were treated with 3% β-alanine in drinking water (taurine depleted) for two months, light exposed or both. Retinal and external thickness were measured in vivo at baseline and pre-processing with Spectral-Domain Optical Coherence Tomography (SD-OCT). Retinal cryostat cross sections were immunodetected with antibodies against various antigens to investigate microglial and macroglial cell reaction, photoreceptor outer segments, synaptic connections and oxidative stress. Taurine depletion caused a decrease in retinal thickness, shortening of photoreceptor outer segments, microglial cell activation, oxidative stress in the outer and inner nuclear layers and the ganglion cell layer and synaptic loss. These events were also observed in light exposed animals, which in addition showed photoreceptor death and macroglial cell reactivity. Light exposure under taurine depletion further increased glial cell reaction and oxidative stress. Finally, the retinal pigment epithelial cells were Fluorogold labeled and whole mounted, and we document that taurine depletion impairs their phagocytic capacity. We conclude that taurine depletion causes cell damage to various retinal layers including retinal pigment epithelial cells, photoreceptors and retinal ganglion cells, and increases the susceptibility of the photoreceptor outer segments to light damage. Thus, beta-alanine supplements should be used with caution.

Highlights

Taurine, a nonessential amino acid very abundant in many mammalian tissues, is highly concentrated in excitable tissues such as the retina [1]
When we compared the numbers of microglial cells in the different retinal layers between the different subgroups, we found that the β-alanine and light-exposed subgroup showed significantly increased numbers of microglial cells than all the other subgroups in all the retinal layers except in the inner nuclear layer (INL) and outer nuclear layer (ONL) layers, where the numbers of microglial cells were similar between all subgroups (Figure 4F), and in the outer segments (OS) layer where it showed significant differences only with the β-alanine non light-exposed subgroup but not with the light-exposed subgroup (Figure 4F)
Our results document that taurine depletion induces glial cell activation and photoreceptor degeneration and oxidative stress to retinal neurons and to retinal ganglion cells and synaptic loss

Summary

Introduction

A nonessential amino acid very abundant in many mammalian tissues, is highly concentrated in excitable tissues such as the retina [1]. Changes in taurine plasma levels are related to vigabatrin (an antiepileptic drug)-induced retinal toxicity in humans and rodents [11,12]. It appears that taurine is essential for retinal development and neuroprotection. The exact mechanisms by which taurine acts in the retina to promote neuronal survival or neuroprotection remain unknown, especially in retinal degenerations, but in the central [11,12].

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