Excess Glutamate May Cause Dilation of Retinal Blood Vessels in Glutamate/Aspartate Transporter-Deficient Mice.

Takayuki Gonome,Saeko Arai,Yuting Xie,Natsuki Maeda-Monai,Reiko Tanabu,Takashi Kudo,Kodai Yamauchi,Mitsuru Nakazawa

doi:10.1155/2019/6512195

Abstract

Purpose To investigate the longitudinal findings of fundus features and spectral-domain optical coherence tomography (SD-OCT) to characterize the morphologic features in a mouse model of defective glutamate/aspartate transporter (GLAST−/− mice). Materials and Methods The fundus findings and SD-OCT images were longitudinally recorded at five time points from postnatal (P) 22 to P156 in GLAST−/− mice. As a control wild type, age-matched C57BL/6J mice were employed. The mouse retina was subdivided into five layers, and the thickness of each layer was longitudinally measured by InSight® using SD-OCT pictures. The SD-OCT findings were compared with the histologic appearances. The diameter of the retinal blood vessels was measured by the ImageJ® software program using SD-OCT images. The data were statistically compared between both age-matched mouse groups. Results The retinal blood vessels appeared more dilated in GLAST−/− mice than in wild-type mice. This tendency was statistically significant at all time points after P44 by analyses using SD-OCT images. The ganglion cell complex (GCC) and outer nuclear layer (ONL) were significantly thinner in GLAST−/− mice at all time points after P80 than in the wild-type mice. This tendency was more clearly indicated by SD-OCT than histologic sections. Discussion In the present study, we found for the first time the dilation of the retinal blood vessels and the thinning of the ONL in GLAST−/− mice, in addition to the thinning of the GCC.

Highlights

Glutamate is a major excitatory neurotransmitter of the mammalian retina, and its uptake is essential for neurotransmission at glutamatergic synapses [1]
Previous studies have shown that the glutamate uptake by glutamate/aspartate transporter (GLAST) into Muller cells provides a substrate for synthesizing glutathione, which is an important radical scavenger composed of a tripeptide of glutamate, cysteine, and glycine
The large retinal blood vessels and retinal capillaries appeared more dilated in GLAST− /− mice than in C57BL/6J mice (Figure 2). ere have been no previous reports describing the characteristics of the fundus findings of GLAST− /− mice

Summary

Introduction

Glutamate is a major excitatory neurotransmitter of the mammalian retina, and its uptake is essential for neurotransmission at glutamatergic synapses [1]. Five subtypes of glutamate transporter are expressed [2]. Glutamate/aspartate transporter (GLAST) is expressed only in Muller cells, and it removes glutamate from the extracellular space [3,4,5,6]. Erefore, deficient or dysfunction of GLAST leads to elevation of glutamate concentration in the retina. Previous studies have shown that the glutamate uptake by GLAST into Muller cells provides a substrate for synthesizing glutathione, which is an important radical scavenger composed of a tripeptide of glutamate, cysteine, and glycine. Erefore, GLAST expressed in Muller cells is essential for keeping the extracellular glutamate concentration below the neurotoxic level and for maintaining the glutathione levels in Muller cells by transporting glutamate into the cells and providing the substrate for glutathione synthesis The glutamate uptake is a rate-limiting step in glial glutathione synthesis [7, 8]. erefore, GLAST expressed in Muller cells is essential for keeping the extracellular glutamate concentration below the neurotoxic level and for maintaining the glutathione levels in Muller cells by transporting glutamate into the cells and providing the substrate for glutathione synthesis

Methods

Results

Conclusion