Correction: Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat.
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SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC9876278 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
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Correction: Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat.
PloS one 20230125 1
[This corrects the article DOI: 10.1371/journal.pone.0264787.]. ...[more]
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Project description:Alterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer's disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion cells, could also be associated with disruption of cholesterol homeostasis. In the present study we characterized cholesterol metabolism in a rat model of laser-induced intraocular hypertension, the main risk factor for glaucoma. Sterol levels were measured using gas-chromatography and cholesterol-related gene expression using quantitative RT-PCR at various time-points. As early as 18 hours after the laser procedure, genes implicated in cholesterol biosynthesis and uptake were upregulated (+49% and +100% for HMG-CoA reductase and LDLR genes respectively, vs. naive eyes) while genes involved in efflux were downregulated (-26% and -37% for ApoE and CYP27A1 genes, respectively). Cholesterol and precursor levels were consecutively elevated 3 days post-laser (+14%, +40% and +194% for cholesterol, desmosterol and lathosterol, respectively). Interestingly, counter-regulatory mechanisms were transcriptionally activated following these initial dysregulations, which were associated with the restoration of retinal cholesterol homeostasis, favorable to ganglion cell viability, one month after the laser-induced ocular hypertension. In conclusion, we report here for the first time that ocular hypertension is associated with transient major dynamic changes in retinal cholesterol metabolism.
| S-EPMC8916636 | biostudies-literature
Project description:Goals of the study: 1. Assess the gene expression profile in rat RGC after experimental IOP elevation to elucidate the molecular mechanisms of RGC death. 2. Identify potentially novel genes and pathways that may contribute to RGC death in glaucoma. Background: Glaucoma is a neurodegenerative disease characterized by the slow, progressive degeneration of RGC. Elevated IOP is the biggest risk factor for developing glaucoma, loss of RGC and optic nerve atrophy. The pathophysiology of glaucomatous neurodegeneration is not fully understood. It is now clear that RGC die by apoptosis in glaucoma. However, what triggers the apoptosis is still unknown. So far, several gene expression studies have been performed on the retina as a whole. These studies revealed up and downregulation of many genes in response to elevated IOP and optic nerve transection. However, the retina is a complex tissue composed of neuronal, glial and vascular cell types. The RGCs only comprise 5% or less of retinal cells. The gene expression profiles from whole retina can not represent of RGC gene expression. In the current study, we sought to investigate the whole genome regulation of the RGCs in glaucoma.
2010-10-01 | GSE12596 | GEO
Project description:PurposeIntraocular pressure (IOP) is an important risk factor in glaucoma. Gene expression changes were studied in glaucomatous rat retinal ganglion cells (RGCs) to elucidate altered transcriptional pathways.MethodsRGCs were back-labeled with Fluorogold. Unilateral IOP elevation was produced by injection of hypertonic saline into the episcleral veins. Laser capture microdissection (LCM) was used to capture an equal number of RGCs from normal and glaucomatous retinal sections. RNA was extracted and amplified, labeled, and hybridized to rat genome microarrays, and data analysis was performed. After selected microarray data were confirmed by RT-qPCR and immunohistochemistry, biological pathway analyses were performed.ResultsSignificant changes were found in the expression of 905 genes, with 330 genes increasing and 575 genes decreasing in glaucomatous RGCs. Multiple cellular pathways were involved. Ingenuity pathway analysis demonstrated significant changes in cardiac beta-adrenergic signaling, interferon signaling, glutamate receptor signaling, cAMP-mediated signaling, chemokine signaling, 14-3-3-mediated signaling, and G-protein-coupled receptor signaling. Gene set enrichment analysis showed that the genes involved in apoptotic pathways were enriched in glaucomatous RGCs. The prosurvival gene Stat3 was upregulated in response to elevated IOP, and immunohistochemistry confirmed that Stat3 and phosphorylated-Stat3 levels were increased in RGCs in experimental glaucoma. In addition, the expression of several prosurvival genes normally expressed in RGCs was decreased.ConclusionsThere are extensive changes in gene expression in glaucomatous RGCs involving multiple molecular pathways, including prosurvival and prodeath genes. The alteration in the balance between prosurvival and prodeath may contribute to RGC death in glaucoma.
| S-EPMC2910641 | biostudies-literature
Project description:Goals of the study: 1. Assess the gene expression profile in rat RGC after experimental IOP elevation to elucidate the molecular mechanisms of RGC death. 2. Identify potentially novel genes and pathways that may contribute to RGC death in glaucoma. Background: Glaucoma is a neurodegenerative disease characterized by the slow, progressive degeneration of RGC. Elevated IOP is the biggest risk factor for developing glaucoma, loss of RGC and optic nerve atrophy. The pathophysiology of glaucomatous neurodegeneration is not fully understood. It is now clear that RGC die by apoptosis in glaucoma. However, what triggers the apoptosis is still unknown. So far, several gene expression studies have been performed on the retina as a whole. These studies revealed up and downregulation of many genes in response to elevated IOP and optic nerve transection. However, the retina is a complex tissue composed of neuronal, glial and vascular cell types. The RGCs only comprise 5% or less of retinal cells. The gene expression profiles from whole retina can not represent of RGC gene expression. In the current study, we sought to investigate the whole genome regulation of the RGCs in glaucoma. The study was carried out in 3 adult male Brown Norway rats with experimental glaucoma. An equal number of RGCs were captured from normal eyes and eyes with elevated IOP. Gene expression in the glaucomatous RGC was compared with that in the fellow RGC by using Affymetrix Gene chip.
2010-10-01 | E-GEOD-12596 | biostudies-arrayexpress
Project description:BackgroundGlaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.MethodsA mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.ResultsWe first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.ConclusionsThese findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
| S-EPMC8705189 | biostudies-literature
Project description:Intraocular pressure was elevated through episkleral vein occlusion by thermic cauterization of SD rats. Animals were further sacrificed after different periods of elevated IOP and the retinal proteins were investigated for alterations regarding the relative protein level in this experimental model of glaucoma.
2017-11-28 | MSV000081757 | MassIVE
Project description:Intraocular pressure was elevated through episkleral vein occlusion by thermic cauterization of SD rats. Animals were further sacrificed after different periods of elevated IOP and the retinal proteins were investigated for alterations regarding the relative protein level in this experimental model of glaucoma.
2017-04-11 | PXD005258 | Pride
Project description:[This corrects the article DOI: 10.1371/journal.pone.0099719.].
| S-EPMC6398837 | biostudies-literature
Project description:PurposeTo study sequential changes in retinal ganglion cell (RGC) morphology in mice after optic nerve crush and after induction of experimental glaucoma.MethodsNerve crush or experimental glaucoma was induced in mice that selectively express yellow fluorescent protein (YFP) in RGCs. Mice were euthanized 1, 4, and 9 days after crush and 1, 3, and 6 weeks after induction of glaucoma by bead injection. All YFP-RGCs were identified in retinal whole mounts. Then confocal images of randomly selected RGCs were quantified for somal fluorescence brightness, soma size, neurite outgrowth, and dendritic complexity (Sholl analysis).ResultsBy 9 days after crush, 98% of RGC axons died and YFP-RGCs decreased by 64%. After 6 weeks of glaucoma, 31% of axons died, but there was no loss of YFP-RGC bodies. All crush retinas combined had significant decreases in neurite outgrowth parameters (P ≤ 0.036, generalized estimating equation [GEE] model) and dendritic complexity was lower than controls (P = 0.017, GEE model). There was no change in RGC soma area after crush. In combined glaucoma data, the RGC soma area was larger than control (P = 0.04, GEE model). At 3 weeks, glaucoma RGCs had significantly larger values for dendritic structure and complexity than controls (P = 0.044, GEE model), but no statistical difference was found at 6 weeks.ConclusionsAfter nerve crush, RGCs and axons died rapidly, and dendritic structure decreased moderately in remaining RGCs. Glaucoma caused an increase in RGC dendrite structure and soma size at 3 weeks.
| S-EPMC3630905 | biostudies-literature
Project description:PurposeTo determine if the optic nerve head (ONH) response to transient elevated intraocular pressure (IOP) can predict the extent of neural loss in the nonhuman primate experimental glaucoma model.MethodsThe anterior chamber pressure of 21 healthy animals (5.4 ± 1.2 years, 8 female) was adjusted to 25 mm Hg for two hours followed by 10 mm Hg for an additional two hours. For the duration of IOP challenge the ONH was imaged using radial optical coherence tomography (OCT) scans at five-minute intervals. Afterward, a randomized sample of 14 of these subjects had unilateral experimental glaucoma induced and were monitored with OCT imaging, tonometry, and ocular biometry at two-week intervals.ResultsWith pressure challenge, the maximum decrease in ONH minimum rim width (MRW) was 40 ± 10.5 µm at 25 mm Hg and was correlated with the precannulation MRW, Bruch's membrane opening (BMO) position, and the anterior lamina cribrosa surface position (P = 0.01). The maximum return of MRW at 10 mm Hg was 16.1 ± 5.0 µm and was not associated with any precannulation ONH feature (P = 0.24). However, healthy eyes with greater thickness return at 10 mm Hg had greater loss of MRW and retinal nerve fiber layer (RNFL) at a cumulative IOP of 1000 mm Hg · days after induction of experimental glaucoma. In addition, MRW and RNFL thinning was correlated with an increase in axial length (P < 0.01).ConclusionThis study's findings suggest that the ONH's response to transient changes in IOP are associated with features of the ONH and surrounding tissues. The neural rim properties at baseline and the extent of axial elongation are associated with the severity of glaucomatous loss in the nonhuman primate model.
| S-EPMC10233313 | biostudies-literature