Background/aims: The goal of the present study was to determine whether transforming growth factor-β(2) (TGF-β(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant α-lipoic acid (LA).
Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-β(2) for 24 h or 200 µM hydrogen peroxide (H(2)O(2)) for 1 h. Lipid peroxidation was measured by a decrease in cis-parinaric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-β(2) or H(2)O(2) exposure. Expressions of the heat shock protein (Hsp) αB-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis.
Results: Both TGF-β(2) and H(2)O(2) increased lipid peroxidation. Treatment of astrocytes with TGF-β(2) and H(2)O(2) upregulated the expression of αB-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-β(2)- and H(2)O(2)-stimulated gene expressions.
Conclusion: We showed that TGF-β(2)- and H(2)O(2)-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy.
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http://dx.doi.org/10.1159/000337835 | DOI Listing |
Purpose: The rat Controlled Elevation of Intraocular pressure (CEI) model allows study of responses to defined intraocular pressures (IOP). In this study, we use Nanostring technology to investigate IOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals.
Methods: Male and female rats (N=35) were subject to CEI for 8-hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.
Exp Eye Res
March 2024
Department of Ophthalmology, Loyola University Chicago, Maywood, IL, 60153, USA; Department of Molecular Pharmacology and Neuroscience, Loyola University Chicago, Maywood, IL, 60153, USA; Research Service, Edward Hines Jr Veterans Affairs Hospital, Hines, IL, 60141, USA. Electronic address:
Prog Retin Eye Res
March 2024
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Glaucoma Center of Excellence, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:
There are many unanswered questions on the relation of intraocular pressure to glaucoma development and progression. IOP itself cannot be distilled to a single, unifying value, because IOP level varies over time, differs depending on ocular location, and can be affected by method of measurement. Ultimately, IOP level creates mechanical strain that affects axonal function at the optic nerve head which causes local extracellular matrix remodeling and retinal ganglion cell death - hallmarks of glaucoma and the cause of glaucomatous vision loss.
View Article and Find Full Text PDFNature
February 2024
Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
The intrinsic mechanisms that regulate neurotoxic versus neuroprotective astrocyte phenotypes and their effects on central nervous system degeneration and repair remain poorly understood. Here we show that injured white matter astrocytes differentiate into two distinct C3-positive and C3-negative reactive populations, previously simplified as neurotoxic (A1) and neuroprotective (A2), which can be further subdivided into unique subpopulations defined by proliferation and differential gene expression signatures. We find the balance of neurotoxic versus neuroprotective astrocytes is regulated by discrete pools of compartmented cyclic adenosine monophosphate derived from soluble adenylyl cyclase and show that proliferating neuroprotective astrocytes inhibit microglial activation and downstream neurotoxic astrocyte differentiation to promote retinal ganglion cell survival.
View Article and Find Full Text PDFRom J Morphol Embryol
November 2023
Discipline of Anatomy, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
Astrocytes (AS) are the most abundant glial cells in the central nervous system (CNS). They have various morphologies and numerous (50-60) branching prolongations, with roles in the maintenance of the CNS function and homeostasis. AS in the optic nerve head (ONH) have specific distribution and function and are involved in the pathogenesis of glaucoma and other neural diseases, modify their morphologies, location, immune phenotype, and ultrastructure, thus being the key players in the active remodeling processes of the ONH.
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