ArticleInvestigative ophthalmology & visual science2014
Neurosteroids are endogenous neuroprotectants in an ex vivo glaucoma model.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
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- Next-Gen Neuroprotection in Glaucoma: Synergistic Molecules for Targeted Therapy.Journal of clinical medicine · 2025Review
- From Neurotransmission to Retinal Pathophysiology: Unraveling the Role of GABA Receptors in Retinal Disease Progression.Journal of neurochemistry · 2025Review
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- Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina.Neural regeneration research · 2023Review
- SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids.Translational psychiatry · 2023Article
- Glaucoma and microglia-induced neuroinflammation.Frontiers in ophthalmology · 2023Review
- The Enantiomer of Allopregnanolone Prevents Pressure-Mediated Retinal Degeneration Via Autophagy.Frontiers in pharmacology · 2022Article
- The neurosteroid allopregnanolone protects retinal neurons by effects on autophagy and GABRs/GABAAutophagy · 2021Article
- Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies.Frontiers in pharmacology · 2021Review
- A lab-on-a-chip model of glaucoma.Brain and behavior · 2020Article
- Inhibitors of cellular stress overcome acute effects of ethanol on hippocampal plasticity and learning.Neurobiology of disease · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeAllopregnanolone is a neurosteroid and powerful modulator of neuronal excitability. The neuroprotective effects of allopregnanolone involve potentiation of γ-aminobutyric acid (GABA) inhibitory responses. Although glutamate excitotoxicity contributes to ganglion cell death in glaucoma, the role of GABA in glaucoma remains uncertain. The aim of this study was to determine whether allopregnanolone synthesis is induced by high pressure in the retina and whether allopregnanolone modulates pressure-mediated toxicity.
methodsEx vivo rat retinas were exposed to hydrostatic pressure (10, 35, and 75 mm Hg) for 24 hours. Endogenous allopregnanolone production was determined by liquid chromatography and tandem mass spectrometry (LC-MS/MS) and immunochemistry. We also examined the effects of allopregnanolone, finasteride, and dutasteride (inhibitors of 5α-reductase), picrotoxin (a GABA(A) receptor antagonist), and D-2-amino-5-phosphonovalerate (APV, a broad-spectrum N-methyl-D-aspartate receptor [NMDAR] antagonist).
resultsPressure loading at 75 mm Hg significantly increased allopregnanolone levels as measured by LC-MS/MS. Elevated hydrostatic pressure also increased neurosteroid immunofluorescence, especially in the ganglion cell layer and inner nuclear layers. Staining was negligible at lower pressures. Enhanced allopregnanolone levels and immunostaining were substantially blocked by finasteride, but more effectively inhibited by dutasteride and APV. Administration of exogenous allopregnanolone suppressed pressure-induced axonal swelling in a concentration-dependent manner, while picrotoxin overcame these neuroprotective effects.
conclusionsThese results indicate that the synthesis of allopregnanolone is enhanced mainly via NMDARs in the pressure-loaded retina, and that allopregnanolone diminishes pressure-mediated retinal degeneration via GABAA receptors. Allopregnanolone and other related neurosteroids may serve as potential novel therapeutic targets for the prevention of pressure-induced retinal damage in glaucoma.
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