Browsing by Subject "optic nerve head"
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Item In Vitro Effect of CNTF, FGF-9, IL-1α on Human Optic Nerve Head Astrocytes(2004-08-01) Tovar-Vidales, Tara; Wordinger, Robert J.; Alvarez-Gonzales, Rafael; Agarwal, NeerajTovar, Tara., In Vitro Effect of CNTF, FGF-9, and IL-1α on Human Optic Nerve Head Astrocytes. Master of Science (Biomedical Sciences), August 2004, 100 pp., 4 tables, 35 illustrations, bibliography, 163 titles. Glaucoma is a leading cause of blindness worldwide. A major risk factor for glaucoma is increased intraocular pressure that leads to pathological changes in the optic nerve head (ONH). Astrocytes within the ONH become activated in glaucoma and may create an environment detrimental to retinal ganglion cell axons. The factors that cause activation of the ONH astrocytes (ONA) are unknown, although there is evidence that CNTF, FGF-9, and IL-1α activate glial cells within the CNS. The purpose of this research was to determine if exogenous CNTF, FGF-9, and/or IL-1α activate human ONH astrocytes.Item Mirna Expression in Glaucomatous and TGFbeta2 Treated Lamina Cribrosa Cells(MDPI, 2021-06-08) Lopez, Navita N.; Rangan, Rajiv; Clark, Abbot F.; Tovar-Vidales, TaraGlaucoma is a group of optic neuropathies that leads to irreversible vision loss. The optic nerve head (ONH) is the site of initial optic nerve damage in glaucoma. ONH-derived lamina cribrosa (LC) cells synthesize extracellular matrix (ECM) proteins; however, these cells are adversely affected in glaucoma and cause detrimental changes to the ONH. LC cells respond to mechanical strain by increasing the profibrotic cytokine transforming growth factor-beta 2 (TGFbeta2) and ECM proteins. Moreover, microRNAs (miRNAs or miR) regulate ECM gene expression in different fibrotic diseases, including glaucoma. A delicate homeostatic balance between profibrotic and anti-fibrotic miRNAs may contribute to the remodeling of ONH. This study aimed to determine whether modulation of miRNAs alters the expression of ECM in human LC cells. Primary human normal and glaucoma LC cells were grown to confluency and treated with or without TGFbeta2 for 24 h. Differences in expression of miRNAs were analyzed using miRNA qPCR arrays. miRNA PCR arrays showed that the miR-29 family was significantly decreased in glaucomatous LC cell strains compared to age-matched controls. TGFbeta2 treatment downregulated the expression of multiple miRNAs, including miR-29c-3p, compared to controls in LC cells. LC cells transfected with miR-29c-3p mimics or inhibitors modulated collagen expression.Item miRNA Profiling of Human Optic Nerve Head Astrocytes Exposed to Cyclic Stretch(2021-05) Rangan, Rajiv S.; Tovar-Vidales, Tara; Clark, Abbot F.; Liu, YangGlaucoma is a leading cause of irreversible blindness. Vision loss results from the degeneration and death of retinal ganglion cells (RGCs) and their axons. The primary risk factor for glaucoma is increased intraocular pressure (IOP) (2). Elevated IOP results in aberrations in the biomechanical properties of ocular tissues - including the transmission of biomechanical stretch through the reticulated, fibroelastic region of the optic nerve head (ONH) known as the lamina cribrosa (LC) (6). Cells of the LC are sensitive to biomechanical stretch and respond to increased stretch and pressure to promote the excessive synthesis of extracellular matrix (ECM) proteins and ECM remodeling (15,17). These responses promote a fibrotic environment within the LC that can cause mechanical damage to the axons of RGCs. ONH astrocytes represent one of the major cell types of the LC and are believed to contribute significantly to pathological ECM remodeling at the LC during glaucoma (11). ONH astrocytes also demonstrate a dysregulated pattern of protein expression when exposed to stretch (17). The mechanism that underlies this stretch-induced, aberrant dysregulation is unknown. MicroRNA (miRNA) dysregulation may represent one of the mechanisms contributing to the differential protein expression patterns seen in ONH astrocytes exposed to stretch. In this study we examine the miRNA profiles of ONH astrocytes exposed to cyclic stretch.Item Stretch stress propels glutamine dependency and glycolysis in optic nerve head astrocytes(Frontiers Media S.A., 2022-08-05) Pappenhagen, Nathaniel; Yin, Eric; Morgan, Autumn B.; Kiehlbauch, Charles C.; Inman, Denise M.Glaucoma is an optic neuropathy that leads to irreversible blindness, the most common subtype of which is typified by a chronic increase in intraocular pressure that promotes a stretch injury to the optic nerve head. In rodents, the predominant glial cell in this region is the optic nerve head astrocyte that provides axons with metabolic support, likely by releasing lactate produced through astrocytic glycolysis. Our primary hypothesis is that stretching of the optic nerve head astrocytes alters their metabolic activity, thereby advancing glaucoma-associated degeneration by compromising the metabolic support that the astrocytes provide to the axons in the optic nerve head. Metabolic changes in optic nerve head astrocytes were investigated by subjecting them to 24 h of 12% biaxial stretch at 1 Hz then measuring the cells' bioenergetics using a Seahorse XFe24 Analyzer. We observed significant glycolytic and respiratory activity differences between control and stretched cells, including greater extracellular acidification and lower ATP-linked respiration, yet higher maximal respiration and spare capacity in stretched optic nerve head astrocytes. We also determined that both control and stretched optic nerve head astrocytes displayed a dependency for glutamine over pyruvate or long-chain fatty acids for fuel. The increased use of glycolysis as indicated by the extracellular acidification rate, concomitant with a dependency on glutamine, suggests the need to replenish NAD + for continued glycolysis and provision of carbon for TCA cycle intermediates. Stretch alters optic nerve astrocyte bioenergetics to support an increased demand for internal and external energy.Item The Role of Transforming Growth Factor Beta 2 Signaling and MicroRNAs in Optic Nerve Head Remodeling(2020-08) Lopez, Navita N.; Clark, Abbot F.; Tovar-Vidales, Tara; Liu, Yang; Pang, Iok-HouPrimary open-angle glaucoma (POAG) is a prevalent age-related neurodegenerative disease of the visual system. There are functional and morphological changes in the retina, optic nerve head (ONH) and brain that lead to an irreversible loss of vision. POAG is characterised by degeneration of retinal ganglion cells (RGC), thinning of the neuro-retinal rim and structural deformation of the ONH. The primary site of injury is the lamina cribrosa, which is a fibro-elastic connective tissue that supports the ONH and unmyelinated RGC axons as they exit the intraocular space. Pathological changes to the lamina cribrosa include posterior displacement of the lamina cribrosa, loss of trophic support, and remodeling of the extracellular matrix (ECM). An important growth factor associated with tissue remodeling is TGFb2. TGFb2 activates the SMAD-dependent TGFb2 pathway and increases transcription of several ECM genes including collagen, fibronectin and crosslinking enzymes. In POAG, the levels of TGFb2 are increased in the lamina cribrosa and is associated with excess deposition of ECM molecules. This study proposes to investigate the intermediary mechanisms that lead to tissue remodeling. microRNAs (miRNAs) regulate gene expression by inhibiting protein translation. We hypothesized that miRNAs are dysregulated in POAG and in response to TGFb2, which leads to excess ECM synthesis and tissue remodeling. We isolated primary human ONH astrocytes and lamina cribrosa cells from POAG and normal donor eyes. We used miRNA PCR arrays to determine differentially expressed miRNAs in POAG and TGFb2 treated cells. Several anti-fibrotic miRNAs were downregulated, including downregulation of miR-29c-3p in POAG and TGFb2 treated lamina cribrosa cells, and downregulation of miR-200b-3p in TGFb2 treated ONH astrocytes. To validate mRNA targets and determine the functional role of differentially expressed miRNAs, we modulated miRNA biology using miRNA mimics and inhibitors. Overexpression of miR-29c-3p and miR-200b- decreased the expression of ECM proteins. Treatment with TGFb2 increased the expression of collagens and fibronectin and overexpression of miR-29c-3p and miR-200b-3p decreased this effect, suggesting that miR-29c-3p and miR-200b-3p regulate the TGFb2 signaling pathway. It is possible that increased TGFb2 is responsible for tissue remodeling through inhibition of anti-fibrotic miRNAs and a subsequent increase in ECM synthesis.