Mirna Expression in Glaucomatous and TGFβ2 Treated Lamina Cribrosa Cells.
Ontology highlight
ABSTRACT:
SUBMITTER: Lopez NN
PROVIDER: S-EPMC8229860 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We determined the differential expression of miRNAs that target extracellular matrix mRNAs in glauocmatous and TGFb2 treated lamina cribrosa cells compared to normal lamina cribrosa cells.
2021-06-15 | GSE178137 | GEO
Project description:MiRNA Expression in Glaucomatous and TGFb2 Treated Lamina Cribrosa cells
| PRJNA737444 | ENA
Project description:The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.
| S-EPMC5940889 | biostudies-other
Project description:Purpose: Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. The authors report the first study of global and ECM-focused gene transcription differentials between GFAP-negative negative lamina cribrosa (LC) cells from normal and POAG human donors. Methods: GFAP-negative LC cell lines were generated from the optic nerve tissue of three normal (n=3) and three POAG (n=3) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was carried out using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. Results: 285 genes were up regulated by greater than 1.5 fold and 413 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, SPARC, periostin, thrombospondin, CRTL-1, CTGF and collagen types I, III, V and VIII. Downregulated ECM genes in POAG included MMP-1, fibulin, decorin and tenacsin XB. All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. Conclusions: This study reports for the first time that POAG LC cells in-vitro demonstrate up regulated ECM and pro-fibrotic gene expression compared with normal LC cells. This may be a pathological characteristic of this cell type in POAG in-vivo. We believe that the LC cell may be a pivotal regulator of optic nerve head ECM remodeling and an attractive target for future therapeutic strategies in POAG.
2009-01-06 | GSE13534 | GEO
Project description:PURPOSE: Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. We report the first study of global and ECM-focused gene transcription differentials between GFAP-negative lamina cribrosa (LC) cells from normal and POAG human donors. METHODS: GFAP-negative LC cell lines were generated from the optic nerve tissue of four normal (n=4) and four POAG (n=4) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was performed using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. RESULTS: 183 genes were upregulated by greater than 1.5 fold and 220 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, transforming growth factor beta 1 (TGFbeta1), secreted acid protein cysteine rich (SPARC), periostin (POSTN), thrombospondin-1 (THBS1), cartilage linking protein-1 (CRTL-1), and collagen type I (COL1A1), collagen type V (COL5A1), and collagen type XI (COL11A1). Downregulated ECM genes in POAG included fibulin 1 (FBLN1), decorin (DCN), and collagen type XVIII (COL18A1). All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. CONCLUSIONS: This study reports for the first time that POAG LC cells in-vitro demonstrate upregulated ECM and pro-fibrotic gene expression compared with normal LC cells. This may be a pathological characteristic of this cell type in POAG in-vivo. We believe that the LC cell may be a pivotal regulator of optic nerve head ECM remodeling in POAG and an attractive target for molecular therapeutic strategies in the future.
| S-EPMC2622717 | biostudies-literature
Project description:PurposeThe lamina cribrosa (LC) is known to play a critical role in the pathogenesis of glaucoma. Although it has been reported that striae-shaped or slit-shaped lamina pores are more frequent in eyes with primary open angle glaucoma (POAG), this observation is based only on fundus photography. The primary object of this study is to perform layer-by-layer comparisons of the shape of lamina pores within the LC in vivo.DesignCross-sectional study.MethodsOptic nerve head B-scans were obtained using custom-made broad-wavelength optical coherence tomography with a mode-locked laser. A total of 300 single B-scans per eye were obtained and three-dimensional images were rendered from these image sequences to obtain 2-μm thin-slice en face images of the LC. Elongation indices (EIs) of the lamina pores were measured from the anterior surface (AS) of the LC to the deeper layers in 40-μm increments.ResultsThirteen eyes from 10 primary open angle glaucoma (POAG) patients of mean deviation -15.2 (-16.5, -12.9) (median [25,75 percentile]) dB and 10 eyes from 7 normal controls were studied. Although the EI value was not significantly different between the superior, temporal and inferior regions of the LC at any depth level in either group, it was greater at the AS than at the 40 μm and 80 μm depth levels (P < .001) in both groups, and was greater in the POAG group only at the AS and 40 μm depth level (P ≤ .05). After adjustment for age and refraction, the effects of depth and presence of POAG on the EI value remained significant. Also, the severity of glaucoma and depth were significant factors associated with EI in multivariate analysis.ConclusionsElongation of lamina pores was significantly more evident at the anterior surface and the 40-μm depth level of the LC in POAG eyes than in normal eyes, suggesting that nerve fiber bundles passing through the LC were under greater stress in the anterior layers of the LC.
| S-EPMC5526571 | biostudies-literature
Project description:PurposeTo investigate whether vessel density assessed by optical coherence tomography angiography (OCT-A) is reduced in glaucomatous eyes with focal lamina cribrosa (LC) defects.DesignCross-sectional, case-control study.ParticipantsA total of 82 patients with primary open-angle glaucoma (POAG) from the Diagnostic Innovations in Glaucoma Study (DIGS) with and without focal LC defects (41 eyes of 41 patients in each group) matched by severity of visual field (VF) damage.MethodsOptical coherence tomography (OCT) angiography-derived circumpapillary vessel density (cpVD) was calculated as the percentage area occupied by vessels in the measured region extracted from the retinal nerve fiber layer (RNFL) in a 750-μm-wide elliptical annulus around the disc. Focal LC defects were detected using swept-source OCT images.Main outcome measuresComparison of global and sectoral (eight 45-degree sectors) cpVDs and circumpapillary RNFL (cpRNFL) thicknesses in eyes with and without LC defects.ResultsAge, global, and sectoral cpRNFL thicknesses, VF mean deviation (MD) and pattern standard deviation, presence of optic disc hemorrhage, and mean ocular perfusion pressure did not differ between patients with and without LC defects (P > 0.05 for all comparisons). Mean cpVDs of eyes with LC defects were significantly lower than in eyes without a defect globally (52.9%±5.6% vs. 56.8%±7.7%; P = 0.013) and in the inferotemporal (IT) (49.5%±10.3% vs. 56.8%±12.2%; P = 0.004), superotemporal (ST) (54.3%±8.8% vs. 58.8%±9.6%; P = 0.030), and inferonasal (IN) (52.4%±9.0% vs. 57.6%±9.1%; P = 0.009) sectors. Eyes with LC defects in the IT sector (n = 33) had significantly lower cpVDs than eyes without a defect in the corresponding IT and IN sectors (P < 0.05 for all). Eyes with LC defects in the ST sector (n = 19) had lower cpVDs in the ST, IT, and IN sectors (P < 0.05 for all).ConclusionsIn eyes with similar severity of glaucoma, OCT-A-measured vessel density was significantly lower in POAG eyes with focal LC defects than in eyes without an LC defect. Moreover, reduction of vessel density was spatially correlated with the location of the LC defect.
| S-EPMC5360451 | biostudies-literature
Project description:Focal lamina cribrosa (LC) defects have been found to play an important role in the development and progression of glaucomatous optic neuropathy. However, the mechanism of generation of focal LC defects is largely unknown. This cross-sectional study was performed to investigate LC curvature and the frequency of parapapillary choroidal microvascular dropout (MvD) in glaucomatous eyes with focal LC defects. This study was conducted by a retrospective review of patients with primary open-angle glaucoma (POAG) included in an ongoing prospective study being performed at the Seoul National University Bundang Hospital (Investigating Glaucoma Progression Study). A total of 118 eyes of 118 patients with POAG, 59 with and 59 without focal LC defects, with eyes matched by age, axial length, and severity of visual field (VF) damage were included. Posterior LC bowing was assessed by calculating LC curvature index (LCCI), as the inflection of a curve representing a section of the LC, on the optic nerve head images obtained by enhanced-depth-imaging (EDI) spectral-domain optical coherence tomography (OCT). MvD was detected by OCT angiography. LCCI and MvD frequency were compared between eyes with and without focal LC defects. Mean LCCI was significantly smaller than in eyes with than without focal LC defects (9.75 ± 1.29 vs. 11.25 ± 1.39, P < 0.001). MvD was significantly more frequent in eyes with than without focal LC defects (84.7% vs. 49.2%, P < 0.001). MvD in eyes with focal LC defects showed a strong topographic correlation with the focal LC defects. These findings suggest that focal LC defects may primarily result from vascular factors rather than from mechanical strain.
| S-EPMC7174329 | biostudies-literature
Project description:PurposeTo test the hypothesis that in healthy human eyes the lamina cribrosa (LC) insertion into the pia mater increases with age.MethodsThe optic nerve heads (ONHs) of donor eyes fixed at either 5 or 50 mm Hg of IOP were sectioned, stained, and imaged under bright- and dark-field conditions. A 3-dimensional (3D) model of each ONH was reconstructed. From the 3D models we measured the area of LC insertion into the peripapillary scleral flange and into the pia, and computed the total area of insertion and fraction of LC inserting into the pia. Linear mixed effect models were used to determine if the measurements were associated with age or IOP.ResultsWe analyzed 21 eyes from 11 individuals between 47 and 91 years old. The LC inserted into the pia in all eyes. The fraction of LC inserting into the pia (2.2%-29.6%) had a significant decrease with age (P = 0.049), which resulted from a nonsignificant increase in the total area of LC insertion (P = 0.41) and a nonsignificant decrease in the area of LC insertion into the pia (P = 0.55). None of the measures was associated with fixation IOP (P values 0.44-0.81). Differences between fellow eyes were smaller than differences between unrelated eyes.ConclusionsThe LC insertion into the pia mater is common in middle-aged and older eyes, and does not increase with age. The biomechanical and vascular implications of the LC insertion into the pia mater are not well understood and should be investigated further.
| S-EPMC3466065 | biostudies-literature
Project description:PurposeTo investigate peripheral lamina cribrosa depth (PLCD) and its vertical-horizontal difference in eyes with primary open-angle glaucoma (POAG).MethodsPatients with POAG (n=90 eyes) and age-matched healthy individuals (n=90 eyes) underwent swept-source optical coherence tomography (SS-OCT) scans centered at the optic discs. The PLCD was defined as the vertical distance between the most peripheral visible end of anterior lamina cribrosa (LC) surface and the reference plane connecting the Bruch's membrane openings. The PLCD in each quadrant region and the vertical-horizontal PLCD difference were compared between the POAG and healthy eyes. The clinical factors associated with increased PLCD were evaluated.ResultsThe PLCD was significantly larger in the POAG eyes than the control eyes at the horizontal (P=0.034) and vertical (P=0.001) meridians. The vertical PLCD was significantly larger than the horizontal PLCD, both in the POAG eyes (P<0.001) and in the control eyes (P=0.003). However, the vertical-horizontal PLCD difference was significantly larger in the POAG eyes (47±60??m) than in the control eyes (18±54??m, P=0.001). Multivariate regression showed a significant association of male gender (P=0.005), increased baseline IOP (P=0.043), and decreased MD of VF (P=0.025) with increased PLCD.ConclusionsThe peripheral LC was displaced more posteriorly in the POAG eyes compared with the age-matched healthy eyes. In the POAG eyes, the peripheral LC was displaced more posteriorly at the vertical meridian than at the horizontal meridian. The peripheral LC in the vertical meridian might have increased IOP-related strain (deformation) compared with horizontal meridian in glaucomatous eyes.
| S-EPMC4815695 | biostudies-literature