TIPARP is involved in the regulation of intraocular pressure
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ABSTRACT:
PROVIDER: PRJNA902418 | ENA |
REPOSITORIES: ENA
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Project description:Previous studies indicated that activation of glial cells and inflammatory responses are triggering factors of glaucomatous optic neuropathy. In particular, neurotoxic reactive astrocytes have been found to play a significant role in retinal ganglion cell damage. Furthermore, research showed that activation of glial cells is not dependent on retinal ganglion cell injury, but rather a direct response to pathological elevation of intraocular pressure. However, the molecular mechanism by which elevated intraocular pressure triggers glial activation through mechanical forces remains unknown. By spatial transcriptome sequencing, our study revealed that the neurotoxic astrocyte would rapidly be reactivated in the optic nerve head under elevated intraocular pressure in vivo.
2024-08-31 | GSE241192 | GEO
Project description:Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. The molecular mechanism of elevated IOP is unclear, which impedes glaucoma therapy. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible Poly-ADP-ribose Polymerase (TIPARP), a member of the PARP family, catalyses mono-ADP-ribosylation. Here we showed that TIPARP was widely expressed in the cornea, trabecular meshwork, iris, retina, optic nerve, sclera, and choroid of human eyes. The expression of TIPARP was significantly upregulated in the blood and trabecular meshwork of patients with primary open angle glaucoma compared with that of healthy controls. Transcriptome analysis revealed that the expression of genes related to extracellular matrix deposition and cell adhesion was decreased in TIPARP-upregulated human trabecular meshwork (HTM) cells. Moreover, western blot analysis showed that collagen types I and IV, fibronectin, and α-SMA were increased in TIPARP downregulated or TIPARP-inhibited HTM cells. In addition, cross-linked actin networks were produced, and vinculin was upregulated in these cells. Subconjunctival injection of the TIPARP inhibitor RBN-2397 increased the IOP in Sprague–Dawley rats. Therefore, we identified TIPARP as a regulator of IOP through modulation of extracellular matrix and cell cytoskeleton proteins in HTM cells. These results indicate that TIPARP is a potential therapeutic target for ocular hypertension and glaucoma.
2022-12-28 | GSE218153 | GEO
Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury. Six- to eight-week old C57Bl/6 male mice were used in this experiment. One eye underwent an elevation in intraocular pressure to 30 mmHg for 1 hour and then allowed to recover for 3 days. The contralateral eye served as a control. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. We used 10 mice to generate five biological replicates for each condition.
2013-05-17 | E-GEOD-40009 | biostudies-arrayexpress
Project description:sptaial transcriptomics of high intraocular pressure and WT rats.
| PRJNA1006718 | ENA
Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury.
2013-05-17 | GSE40009 | GEO
Project description:Interventions: Group 1: Patients with prostate cancer and planned radical prostatectomy
Contact-free examinations:
x. Determination of refraction and visual acuity
xi. Slit lamp finding (phak / pseudophak), anomalies of the anterior segment affecting the measurability or height of the IOD
xii. Pupillometry (pupil width with and without glare, medically unaffected, possibly latency, constriction and dilatation rate)
xiii. HRT for glaucoma exclusion
xiv. Visante-OCT for corneal thickness measurement
Examinations with contact to the eye
xv. Intraocular pressure using Pascal tonometer and time of measurement (preferably at 03:00pm +/- 1 hour)
xvi. Intraocular pressure using Goldmann tonometer and time of measurement (preferably at 03:00pm +/- 1 hour)
Other investigations
xvii. Blood sample (if possible, combine with clinical routine blood sampling at the Department of Urology)
xviii. urine sample
Group 2: Patients without cancer
Contact-free examinations:
x. Determination of refraction and visual acuity
xi. Slit lamp finding (phak / pseudophak), anomalies of the anterior segment affecting the measurability or height of the IOD
xii. Pupillometry (pupil width with and without glare, medically unaffected, possibly latency, constriction and dilatation rate)
xiii. HRT for glaucoma exclusion
xiv. Visante-OCT for corneal thickness measurement
Examinations with contact to the eye
xv. Intraocular pressure using Pascal tonometer and time of measurement (preferably at 03:00pm +/- 1 hour)
xvi. Intraocular pressure using Goldmann tonometer and time of measurement (preferably at 03:00pm +/- 1 hour)
Other investigations
xvii. Blood sample (if possible, combine with clinical routine blood sampling at the Departme
Primary outcome(s): Does the intraocular pressure differ between patients with prostate cancer and a healthy comparison group? Does the intraocular pressure in prostate cancer, breast cancer or colorectal cancer patients change after surgical tumor removal compared to preoperative values? Is there a difference in systemic levels of potential chemical mediator between prostate cancer patients and a healthy comparison group? Do the absolute values and their postoperative change correlate with the intraocular pressure?
After completing the recruitment, the data of all four patient groups are evaluated with the program STATISTICA (StatSoft).
Study Design: Allocation: Non-randomized controlled study; Masking: Open (masking not used); Control: Other; Assignment: parallel; Study design purpose: diagnostic
| 2434903 | ecrin-mdr-crc
Project description:Elevated intraocular pressure is considered a major cause of glaucomatous retinal neurodegeneration. To facilitate a better understanding of the underlying molecular processes and mechanisms, we report a study focusing on alterations of the retina proteome by induced ocular hypertension in a rat model of the disease. Glaucomatous processes were modelled through sclerosing the aqueous outflow routes of the eyes by hypertonic saline injections into an episcleral vein. Mass spectrometry-based quantitative retina proteomics using a label-free shotgun methodology identified over 200 proteins significantly affected by ocular hypertension. Various facets of glaucomatous pathophysiology were revealed through the organization of the findings into protein interaction networks and by pathway analyses. Concentrating on retinal neurodegeneration as a characteristic process of the disease, elevated intraocular pressure-induced alterations in the expression of selected proteins were verified by targeted proteomics based on nanoflow liquid chromatography coupled with nanoelectrospray ionization tandem mass spectrometry using the parallel reaction monitoring method of data acquisition. Acquired raw data are shared through deposition to the ProteomeXchange Consortium making a retina proteomics dataset on the selected animal model of glaucoma available for the first time.
2023-10-24 | PXD042729 | Pride
Project description:Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. The molecular mechanism of elevated IOP is unclear, which impedes glaucoma therapy. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible Poly-ADP-ribose Polymerase (TIPARP), a member of the PARP family, catalyses mono-ADP-ribosylation. Here we showed that TIPARP was widely expressed in the cornea, trabecular meshwork, iris, retina, optic nerve, sclera, and choroid of human eyes. The expression of TIPARP was significantly upregulated in the blood and trabecular meshwork of patients with primary open angle glaucoma compared with that of healthy controls. Transcriptome analysis revealed that the expression of genes related to extracellular matrix deposition and cell adhesion was decreased in TIPARP-upregulated human trabecular meshwork (HTM) cells. Moreover, western blot analysis showed that collagen types I and IV, fibronectin, and α-SMA were increased in TIPARP-downregulated or TIPARP-inhibited HTM cells. In addition, cross-linked actin networks were produced, and vinculin was upregulated in these cells. Subconjunctival injection of the TIPARP inhibitor RBN-2397 increased the IOP in Sprague-Dawley rats. Therefore, we identified TIPARP as a regulator of IOP through modulation of extracellular matrix and cell cytoskeleton proteins in HTM cells. These results indicate that TIPARP is a potential therapeutic target for ocular hypertension and glaucoma.
| S-EPMC9763400 | biostudies-literature
Project description:Genome-wide association study finds multiple loci associated with intraocular pressure in HS rats
| PRJNA830468 | ENA
Project description:The optic nerve is an important tissue in glaucoma and the unmyelinated nerve head region remains an important site of many early neurodegenerative changes. In humans and mice, astrocytes constitute the major glial cell type in the region, and in glaucoma they become reactive, influencing the optic nerve head (ONH) microenvironment and disease outcome. To determine the response of ONH astrocytes in glaucoma, we studied their transcriptional response to an elevation in intraocular pressure (IOP) induced by the microbead occlusion model. We also assessed the response of astrocytes in the more distal myelinated optic nerve proper (ONP). In this experimental model, astrocytes of the optic nerve exhibited a region-specific and temporally distinct response: ONH astrocytes showed very few early transcriptional changes and ONP astrocytes demonstrated substantially larger changes over the course of the experiment.
2023-10-01 | GSE237073 | GEO