scholarly journals Individual molecular response to elevated intraocular pressure in perfused postmortem human eyes

2009 ◽  
Vol 38 (2) ◽  
pp. 205-225 ◽  
Author(s):  
Núria Comes ◽  
Teresa Borrás

Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. In the clinic, the response to elevated pressure and thus the risk for development of glaucoma differs among individuals. We took advantage of our ability to subject postmortem human eyes from the same individual to physiological and elevated pressure in a perfused outflow model and compared individual patterns of gene expression under pressure. The architecture of the trabecular meshwork, tissue responsible for the maintenance of IOP, was conserved. We performed two sets of experiments. The first set ( n = 5, 10 eyes) used Affymetrix GeneChips, identified the 20 most pressure-altered genes in each individual, and compared their pressure response in the other four. The second set ( n = 5, 10 eyes) selected 21 relevant trabecular meshwork genes and examined, by real-time TaqMan-PCR, the rank of their abundance and of their pressure differential expression in each individual. The majority of the up- and downregulated top-changers of each individual showed an individual response trend. Few genes were general responders. Individual responders included STATH, FBN2, TF, OGN, IL6, IGF1, CRYAB, and ELAM1 (marker for glaucoma). General responders included MMP1, MMP10, CXCL2, and PDPN. In addition, we found that although the relative abundance of selected genes was very similar among nonstressed individuals, the response to pressure of those same genes had a marked individual component. Our results offer the first molecular insight on the variation of the individual response to IOP observed in the clinical setting.

2021 ◽  
Author(s):  
Saidas Nair ◽  
Chitrangda Srivastava ◽  
Robert V Brown ◽  
Swanand Koli ◽  
Helene Choquet ◽  
...  

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.


PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0167364 ◽  
Author(s):  
Shandiz Tehrani ◽  
Lauren Davis ◽  
William O. Cepurna ◽  
Tiffany E. Choe ◽  
Diana C. Lozano ◽  
...  

Author(s):  
Steven J. Folz ◽  
Hiayan Gong ◽  
Darryl R. Overby

Glaucoma is a leading cause of blindness, and elevated intraocular pressure (IOP) characteristic of glaucoma is caused by increased aqueous humor outflow resistance. Studies have localized the bulk of outflow resistance to particular regions along the outflow pathway — namely, the inner wall endothelium of Schlemm’s canal and its underlying juxtacanalicular tissue (JCT) [1] — but the hydrodynamic details of how aqueous humor flows through these tissues and how these tissues generate outflow resistance are not well understood.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
K. Saidas Nair ◽  
Chitrangda Srivastava ◽  
Robert V. Brown ◽  
Swanand Koli ◽  
Hélène Choquet ◽  
...  

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.


2012 ◽  
Vol 05 (01) ◽  
pp. 33
Author(s):  
Marc Töteberg-Harms ◽  
Peter P Ciechanowski ◽  
Jens Funk ◽  
◽  
◽  
...  

Usually an elevated drainage resistance is responsible for elevated intraocular pressure (IOP) in glaucoma, while aqueous humor production is still normal. Therefore, currently there are great efforts to develop surgical techniques that enhance the conventional outflow through the trabecular meshwork and Schlemm’s canal and into the episcleral veins. One of these techniques is excimer laser trabeculotomy (ELT). ELT is easy to perform at the end of cataract surgery. The duration of cataract surgery is only prolonged by 2–3 minutes. IOP can be reduced by up to 34.7 %. It is known that the effect of IOP reduction is constant over time, unlike argon or selective laser trabeculoplasty. The procedure is also very safe. If required later, filtering surgery is not compromised because there is no conjunctival touch during ELT and therefore no scarring of the conjunctiva is induced. For a selected cohort of glaucoma patients, this procedure may avoid the need for trabeculectomy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maiko Maruyama-Inoue ◽  
Tatsuya Inoue ◽  
Shaheeda Mohamed ◽  
Yoko Kitajima ◽  
Shoko Ikeda ◽  
...  

AbstractThe purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.


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