?-Aminoadipic acid protects against retinal disruption through attenuating Muller cell gliosis in a rat model of acute ocular hypertension.

ABSTRACT: Ocular hypertension is an important risk factor for glaucoma. The purpose of this study was to investigate the gliotoxic effects of ?-aminoadipic acid (AAA) in a rat model of AOH and its underlying mechanisms.In the rat model of acute ocular hypertension (AOH), intraocular pressure was increased to 110 mmHg for 60 minutes. Animals were divided into four groups: sham operation (Ctrl), AOH, AOH + phosphate-buffered saline (PBS), and AOH + AAA. Cell apoptosis in the ganglion cell layer was detected with the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay, and retinal ganglion cells (RGCs) immunostained with Thy-1 were counted. Müller cell activation was detected using immunostaining with glutamine synthetase and glial fibrillary acidic protein. Tumor necrosis factor-? (TNF-?) was examined using Western blot.In the rat model of AOH, cell apoptosis was induced in the ganglion cell layer and the number of RGCs was decreased. Müller cell gliosis in the retinas of rats was induced, and retinal protein levels of TNF-? were increased. Intravitreal treatment of AAA versus PBS control attenuated these retinal abnormalities to show protective effects in the rat model of AOH.In the retinas of the rat model of AOH, AAA treatment attenuated retinal apoptosis in the ganglion cell layer and preserved the number of RGCs, likely through the attenuation of Müller cell gliosis and suppression of TNF-? induction. Our observations suggest that AAA might be a potential therapeutic target in glaucoma.

SUBMITTER: Wang X 

PROVIDER: S-EPMC5076852 | biostudies-other | 2016

REPOSITORIES: biostudies-other