scholarly journals GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans

2021 ◽  
Author(s):  
Saidas Nair ◽  
Chitrangda Srivastava ◽  
Robert V Brown ◽  
Swanand Koli ◽  
Helene Choquet ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Anterior Chamber ◽  
Trabecular Meshwork ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Transcriptional Factor ◽  
Histopathological Analysis ◽  
Resonance Imaging ◽  
Progressive Degeneration ◽  
Elevated Intraocular Pressure

Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Kruppel-like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P=4.73x10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.

scholarly journals GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
K. Saidas Nair ◽  
Chitrangda Srivastava ◽  
Robert V. Brown ◽  
Swanand Koli ◽  
Hélène Choquet ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Anterior Chamber ◽  
Trabecular Meshwork ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Transcriptional Factor ◽  
Histopathological Analysis ◽  
Resonance Imaging ◽  
Progressive Degeneration ◽  
Elevated Intraocular Pressure

AbstractChronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel-like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P = 4.73 × 10−6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.

scholarly journals What was Glaucoma Called before the 20th Century?

2015 ◽  
Vol 7 ◽  
pp. OED.S32004 ◽  
Author(s):  
Christopher T. Leffler ◽  
Stephen G. Schwartz ◽  
Francesca M. Giliberti ◽  
Matthew T. Young ◽  
Dennis Bermudez
Keyword(s):  
Intraocular Pressure ◽  
Optic Neuropathy ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
The Other ◽  
Angle Closure ◽  
Open Angle ◽  
Poor Vision ◽  
Elevated Intraocular Pressure

Glaucoma involves a characteristic optic neuropathy, often with elevated intraocular pressure. Before 1850, poor vision with a normal eye appearance, as occurs in primary open-angle glaucoma, was termed amaurosis, gutta serena, or black cataract. Few observers noted palpable hardness of the eye in amaurosis. On the other hand, angle-closure glaucoma can produce a green or gray pupil, and therefore was called, variously, glaucoma (derived from the Greek for glaucous, a nonspecific term connoting blue, green, or light gray) and viriditate oculi. Angle closure, with palpable hardness of the eye, mydriasis, and anterior prominence of the lens, was described in greater detail in the 18th and 19th centuries. The introduction of the ophthalmoscope in 1850 permitted the visualization of the excavated optic neuropathy in eyes with a normal or with a dilated greenish-gray pupil. Physicians developed a better appreciation of the role of intraocular pressure in both conditions, which became subsumed under the rubric “glaucoma”.

scholarly journals Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yogapriya Sundaresan ◽  
Lakshmi Priya Manivannan ◽  
Shanthi Radhakrishnan ◽  
Krishnadas Subbiah Ramasamy ◽  
Muthukkaruppan Veerappan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Trabecular Meshwork ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Stem Cell Marker ◽  
Histopathological Analysis ◽  
Open Angle ◽  
Cell Marker ◽  
Schlemm’S Canal ◽  
Schlemm's Canal

AbstractWe previously identified and characterized human trabecular meshwork stem cells (TMSCs) based on high expression of ABCG2/p75 positivity and high nucleus to cytoplasmic ratio. These TMSCs expressing high ABCG2 and p75 were located to the insert region of the human TM. Additionally, we demonstrated an age-related reduction in the TMSC content which was significantly associated with TM cell loss. In continuation, this study was aimed to determine the TMSC content in glaucomatous donor eyes wherein a drastic reduction in TM cellularity has already been reported. Anterior segments from known glaucomatous (n = 6) and age-matched normal (n = 8) donors were dissected into four quadrants. A minimum of three sections from each quadrant were used for histopathological analysis as well as immunostaining. Analysis of hematoxylin and eosin-stained sections from glaucomatous tissues revealed a decrease in total TM cellularity, thickening of trabecular beams, fusion of trabeculae, absence of patent Schlemm’s canal compared to age-matched controls. In addition, the TM thickness at various positions of the meshwork and the coronal as well as the meridional diameters of the Schlemm’s canal were observed to be significantly reduced in glaucomatous eyes. Further, sections from both the groups were immunostained for universal stem cell marker ABCG2 and neural crest derived stem cell marker p75. The images were acquired using Leica SP8 confocal microscope. Quantification of total TM cellularity based on nuclear counterstain (mean ± SD) using ImageJ identified 69.33 ± 12.77 cells/section in control eyes. In glaucomatous donors, the TM cellularity was found to be reduced significantly to 41.83 ± 9.0 (p = 0.0007). In addition, a reduction in the percentage of TMSCs (cells with high ABCG2 expression and p75 positivity) was evident in glaucomatous donors (0.14 ± 0.17%) compared to age-matched controls (4.73 ± 5.46%) (p = 0.064). Thus, the present study confirmed the significant decline in TM cellularity and a reducing trend in the TMSC content, though this reduction was non-significant in glaucomatous donor eyes. Further studies are essential to elucidate the role of TMSCs in the pathogenesis of primary open angle glaucoma.

scholarly journals Identification of a novel MYOC variant in a Hispanic family with early-onset primary open-angle glaucoma with elevated intraocular pressure

2019 ◽  
Vol 5 (6) ◽  
pp. a004374
Author(s):  
June Criscione ◽  
Weizhen Ji ◽  
Lauren Jeffries ◽  
James M. McGrath ◽  
Scott Soloway ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Early Onset ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Elevated Intraocular Pressure ◽  
Hispanic Family

scholarly journals Optical coherence tomography in the evaluation of structural changes in primary open-angle glaucoma with and without elevated intraocular pressure

2016 ◽  
Vol 73 (7) ◽  
pp. 618-625
Author(s):  
Marija Trenkic-Bozinovic ◽  
Gordana Zlatanovic ◽  
Predrag Jovanovic ◽  
Dragan Veselinovic ◽  
Jasmina Djordjevic-Jocic ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Intraocular Pressure ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Optical Coherence ◽  
Open Angle ◽  
Significant Information ◽  
Rnfl Thickness ◽  
Significant Difference ◽  
Elevated Intraocular Pressure

Background/Aim. Glaucoma is a progressive optic neuropathy characterized by damage of the retinal ganglion cells and their axons and glial cells. The aim of this study was to evaluate the differences and connections between changes in the visual field and the thickness of the peripapillary retinal nerve fiber layer (RNFL), using optical coherence tomography (OCT) in patients with primary open-angle glaucoma with normal and elevated intraocular pressure (IOP). Methods. This prospective study included 38 patients (38 eyes) with primary open-angle glaucoma with normal intraocular pressure (NTG) and 50 patients (50 eyes) with primary open-angle glaucoma with elevated intraocular pressure (HTG), paired by the same degree of structural glaucomatous changes in the optic nerve head and by age. OCT protocols ?fast RNFL thickness? and ?fast optic disc? were used for testing. The patients? age, gender, best corrected visual acuity (BCVA), IOP, stereometric and functional parameters were compared. Results. The average age of the examined population was 65.49 ? 9.36 (range 44-83) years. There was no statistically significant difference by age and by gender between the two study groups (p = 0.795 and p = 0.807, respectively). BCVA was higher in patients with NTG but there was no statistically significant difference compared to HTG patients (p = 0.160). IOP was statistically significantly higher in patients with HTG compared to NTG patients (17.40 ? 2.77 mmHg vs 14.95 ? 3.01 mmHg, p = 0.009). The cup/disc (C/D) (p = 0.258), mean deviation (MD) (p = 0.477), corrected patern standard deviation (CPSD) (p = 0.943), disk area (p = 0.515), rim area (p = 0.294), rim volume (p = 0.118), C/D area R (p = 0.103), RNFL Average (p = 0.632), RNFL Superior (p = 0.283) and RNFL Inferior (p = 0.488) were not statistically significantly different between the groups. Conclusion. OCT measurements of the RNFL thickness provide clinically significant information in monitoring of glaucomatous changes. There are no differences in the patterns of RNFL defects per sectors and quadrants between NTG and HTG, measured by OCT.

scholarly journals Changes in the retrobulbar arterial circulation after decrease of elevated intraocular pressure in patients with primary open angle glaucoma

2011 ◽  
Vol 139 (11-12) ◽  
pp. 718-721 ◽  
Author(s):  
Ivan Marjanovic ◽  
Ana Sundic ◽  
Milija Mijajlovic ◽  
Nadezda Covickovic-Sternic ◽  
Djordje Kontic ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Arterial Circulation ◽  
Haemodynamic Parameters ◽  
Elevated Intraocular Pressure ◽  
Clinical Centre ◽  
Ciliary Arteries ◽  
Retinal Artery

Introduction. An altered perfusion of the optic nerve head has been proposed as a pathogenic factor in glaucoma. Objective. To evaluate changes of haemodynamic parameters in the retrobulbar arterial circulation after a decrease of elevated intraocular pressure (IOP) in patients with primary open angle glaucoma (POAG). Methods. Twenty-six patients were examined, 14 men and 12 women, 21 up to 50 years old and 5 below, all with previously diagnosed and treated POAG, and all examined at the Eye Clinic, Clinical Centre of Serbia. IOP was measured both with a Goldmann aplanation tonometer and dynamic contour tonometer. Central corneal thickness was measured with ultrasound pachymeter. Imaging of the retrobulbar arterial circulation by colour Doppler was performed at the Neurology Clinic, Clinical Centre of Serbia. It involved measuring of haemodynamic parameters of the ophthalmic artery, central retinal artery, and posterior ciliary arteries. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured, and resistive index (RI) and pulsatility index (PI) were calculated. Results. Haemodynamic arterial parameters PSV and EDV in the ophthalmic and central retinal artery after decrease of IOP were lower, while RI and PI were higher. In the posterior ciliary arteries PSV, EDV and PI were lower, and RI was higher. Conclusion. Changes of the retrobulbar arterial circulation after elevated IOP in POAG patients are important for approach and treatment, while the role of vascular factors in the supplement of the optic disc neuroretinal rim could be a key for progression backlash of glaucoma and the radix of neuroprotection.

Sign in / Sign up

Export Citation Format

Share Document