The effects of light, 2-amino-4-phosphonobutyric acid (APB), and kainic acid on rat retinal gamma-aminobutyric acid (GABA)-ergic transmission were studied by measuring levels of retinal GABA following subcutaneous injection of gabaculine, an irreversible inhibitor of GABA-transaminase. Post-gabaculine levels of retinal GABA in light-exposed rats were significantly greater than those in rats held in darkness. The synaptic mechanism of this effect of light was examined by measuring post-gabaculine levels of retinal GABA in rats placed into either lighted or darkened conditions after receiving unilateral intravitreal injections of APB, a glutamate analogue that selectively decreases the activity of ON synaptic pathways in the retina. APB attenuated the post-gabaculine accumulation of GABA in rats held in the light, but not in those placed into darkness. Furthermore, the light-dependent increment in post-gabaculine accumulation of retinal GABA was entirely APB sensitive, and the effect of APB was entirely light dependent. In contrast to APB, kainic acid stimulated the post-gabaculine accumulation of retinal GABA in vivo. Our findings suggest that APB and kainic acid influence GABAergic transmission at different sites in the retina and that some retinal GABAergic neurons are either ON or ON-OFF amacrine cells.
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Sci Total Environ
January 2025
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, 100012 Beijing, China. Electronic address:
Methylmercury (MeHg) is a neurotoxicant with adverse effects on visual systems from fish to man. Clinical signs of visual deficits including color-vision alterations, visual field constriction and blindness have been frequently identified in patients and affected animals following acute and chronic exposure to MeHg. However, it is still unclear whether MeHg causes developmental defects in the eye.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Ophthalmology, Columbia University, New York, NY, USA.
Best1 and Best2 are two members of the bestrophin family of anion channels critically involved in the prevention of retinal degeneration and maintenance of intraocular pressure, respectively. Here, we solved glutamate- and γ-aminobutyric acid (GABA)-bound Best2 structures, which delineate an intracellular glutamate binding site and an extracellular GABA binding site on Best2, respectively, identified extracellular GABA as a permeable activator of Best2, and elucidated the co-regulation of Best2 by glutamate, GABA and glutamine synthetase in vivo. We further identified multiple small molecules as activators of the bestrophin channels.
View Article and Find Full Text PDFMol Neurobiol
December 2024
Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Retinal ischemia-reperfusion injury (RIRI) is a pathological process that occurs in various blinding eye diseases and is often accompanied by anxiety and depression. However, the underlying metabolic mechanism of mood disorders remains unclear. This study aimed to investigate the metabolic dynamics of the brain after RIRI.
View Article and Find Full Text PDFPeerJ
November 2024
Department of Psychiatry, Institute of Health Sciences, İzmir Democracy University, İzmir, Turkey.
Background: Pregabalin abuse is a rapidly growing health problem worldwide, and little is known about the effects of prolonged high-dose use in patients with pregabalin use disorder.
Objective: In this study, the effects of pregabalin abuse on retinal layers were investigated in patients with pregabalin use disorder (PGUD).
Methods: This study included 35 controls and 34 patients with PGUD, according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria.
Life Sci
January 2025
Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Hyperbaric oxygen therapy (HBOT) elevates the partial pressure of life-sustaining oxygen (pO), thereby saving lives. However, HBOT can also cause toxic effects like lung and retinal damage (peripheral oxygen toxicity) and violent myoclonic seizures (central nervous system (CNS) toxicity). The mechanisms behind these effects are not fully understood, hindering the development of effective therapies and preventive strategies.
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