Pathogenesis of Increased Intraocular Pressure in Primary Open‑Angle Glaucoma: Literature Review

Introduction. Despite the high socio-economic significance of primary open-angle glaucoma (POAG), the etiotropic and pathogenetic treatment of this disorder has not yet been implemented, since the mechanisms of the development of this disease are not fully known and understood. One of the topical issues is the pathogenesis of ophthalmic hypertension in POAG.Purpose. To summarize the currently known mechanisms of ophthalmic hypertension in POAG to search for potential molecular targets for pathogenetic pharmacotherapy.Materials and methods. Analysis of publications on PubMed, Medline and eLibrary.Results. Ophthalmic hypertension in POAG emerges due to increased resistance to aqueous humor (AH) outflow. It is caused by increased stiffness of Schlemm’s canal endothelium and trabecular meshwork as a result of changes in the structure and biomechanical properties of its cells and extracellular matrix. These changes are determined by the interaction of signaling molecules in the form of a pathological circle, the main links of which are TGF-β2 and its receptor, Smad 2/3/4, YAP/TAZ, sFRP-1 and CTGF.Conclusion. The cause of ophthalmic hypertension in POAG is fibrosis of the trabecular meshwork. This pathological process is based on the interaction of proteins, the main of which are TGF-β2 and its receptor, Smad 2/3/4, YAP/TAZ, sFRP-1 and CTGF. These molecules can become promising targets for the pathogenetic pharmacological therapy of POAG.

Download Full-text

The Effect of Hyaluronic Acid on MMP-9 Expression in Trabecular Meshwork Cell Culture of Patient with Primary Open Angle Glaucoma

Journal of Agromedicine and Medical Sciences ◽

10.19184/ams.v3i1.4096 ◽

2017 ◽

Vol 3 (1) ◽

pp. 38

Author(s):

Cicih Komariah ◽

Ma’sum Effendi ◽

Hidayat Sujuti

Keyword(s):

Cell Culture ◽

Extracellular Matrix ◽

Hyaluronic Acid ◽

Trabecular Meshwork ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Open Angle ◽

Trabecular Meshwork Cell ◽

Matrix Deposition ◽

Extracellular Matrix Deposition

In primary open angle glaucoma, decrease of hyaluronic acid level is related to extracellular matrix deposition of trabecular meshwork. Extracellular matrix deposition will increase humor aqueous outflow resistance which in turn increase the intraocular pressure. MMP-9 as one of matrix metalloproteinase (MMP) family, has a high potency to degrade the extracellular matrix. The expression of MMP-9 can be activated by hyaluronic acid through its binding with CD44 as hyaluronic main receptor. The aim of this research is to determine the effect of hyaluronic acid on MMP-9 expression in trabecular meshwork cell culture of patient with primary open angle glaucoma by immunocytochemical method. Trabecular meshwork cell culture were exposed to hyaluronic acid at four different concentration (0mg/ml, 1 mg/mL, 3 mg/mL, 6 mg/mL). After 24 hours incubated, we find a significant difference of MMP-9 expression between control group and group with hyaluronic acid. There was significant correlation between hyaluronic acid and MMP-9 expression. Hyaluronic acid exposure will increase MMP-9 expression in trabecular meshwork cell culture. This finding suggest that hyaluronic acid can influence the resistance of humor aqueous outflow in trabecular meshwork by up-regulating MMP-9 expression, and therefore will increase extracellular matrix degradation.Key words : hyaluronic acid, primary open angle glaucoma, MMP-9

Download Full-text

Freeze-controlled Crystallisation of the Aqueous Humour in Glaucomatous and Non-glaucomatous Patients

European Ophthalmic Review ◽

10.17925/eor.2010.04.01.29 ◽

2010 ◽

Vol 04 (01) ◽

pp. 29

Author(s):

Christoph Faschinger ◽

Franz Rabensteiner Dieter ◽

Christian Eberle ◽

Georg Mossböck ◽

Otto Schmut ◽

...

Keyword(s):

Extracellular Matrix ◽

Trabecular Meshwork ◽

Aqueous Humour ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Pigmentary Glaucoma ◽

Multifactorial Disease ◽

Open Angle ◽

Microscope Slide ◽

Trabecular Meshwork Cells

The purpose of this study was to investigate the aqueous humour of glaucomatous and non-glaucomatous patients by freeze-controlled crystallisation qualitatively to detect a possible difference. Aqueous humour was taken from 20 patients with different kinds of glaucoma (11 primary open-angle glaucoma, eight pseudo-exfoliation glaucoma, one pigmentary glaucoma) and compared with samples from 40 patients with cataracts and to samples from seven patients with cataract and glaucoma; 1μl of each sample was applied to a microscope slide and put in a deep-freezer at a constant temperature of -20°C for 24 hours. During this time, the water evaporated and distinct crystal patterns developed. These patterns were examined stereo-microscopically, stored digitally and compared with each other. Many distinct crystals of different sizes and formations were obtained. No obvious differences in the crystal patterns could be found between the three groups (patients with glaucoma, cataract or cataract and glaucoma). As a multifactorial disease, open-angle glaucoma is characterised by specific changes to the trabecular meshwork cells with an accumulation of deposits of extracellular matrix. Since the trabeculum is rinsed consistently by aqueous humour, changes of the compounds might influence these cells. Alterations concerning this were published. In contrast to the ferning test, one of several methods of examining fluids with patterns that are highly dependent on temperature and humidity, our examinations with freeze-controlled crystallisation at a constant and controlled temperature of – 20°C gave more valid results. In our study we could not find obvious differences in the crystal patterns of patients with cataract, glaucoma or cataract and glaucoma.

Download Full-text

Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

PLoS ONE ◽

10.1371/journal.pone.0145824 ◽

2016 ◽

Vol 11 (1) ◽

pp. e0145824 ◽

Cited By ~ 27

Author(s):

Xiaoqin Yan ◽

Mu Li ◽

Zhiqi Chen ◽

Ying Zhu ◽

Yinwei Song ◽

...

Keyword(s):

Comparative Study ◽

Trabecular Meshwork ◽

High Frequency ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Ultrasound Biomicroscopy ◽

Open Angle ◽

High Frequency Ultrasound ◽

Schlemm's Canal ◽

Frequency Ultrasound

Download Full-text

Neuroinflammation in Primary Open-Angle Glaucoma

Journal of Clinical Medicine ◽

10.3390/jcm9103172 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3172 ◽

Cited By ~ 1

Author(s):

Stefania Vernazza ◽

Sara Tirendi ◽

Anna Maria Bassi ◽

Carlo Enrico Traverso ◽

Sergio Claudio Saccà

Keyword(s):

Oxidative Stress ◽

Immune Response ◽

Trabecular Meshwork ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Glaucoma Surgery ◽

Open Angle ◽

Antioxidant Defences ◽

Age Related ◽

Wide Range

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increasing evidence suggests oxidative damage and immune response defects are key factors contributing to glaucoma onset. Indeed, both the failure of the trabecular meshwork tissue in the conventional outflow pathway and the neuroinflammation process, which drives the neurodegeneration, seem to be linked to the age-related over-production of free radicals (i.e., mitochondrial dysfunction) and to oxidative stress-linked immunostimulatory signaling. Several previous studies have described a wide range of oxidative stress-related makers which are found in glaucomatous patients, including low levels of antioxidant defences, dysfunction/activation of glial cells, the activation of the NF-κB pathway and the up-regulation of pro-inflammatory cytokines, and so on. However, the intraocular pressure is still currently the only risk factor modifiable by medication or glaucoma surgery. This present review aims to summarize the multiple cellular processes, which promote different risk factors in glaucoma including aging, oxidative stress, trabecular meshwork defects, glial activation response, neurodegenerative insults, and the altered regulation of immune response.

Download Full-text

Role of Fibronectin in Primary Open Angle Glaucoma

Cells ◽

10.3390/cells8121518 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1518 ◽

Cited By ~ 6

Author(s):

Jennifer A. Faralli ◽

Mark S. Filla ◽

Donna M. Peters

Keyword(s):

United States ◽

Trabecular Meshwork ◽

Vision Loss ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

The United States ◽

Open Angle ◽

Cell Matrix ◽

Fibronectin Fibrils

Primary open angle glaucoma (POAG) is the most common form of glaucoma and the 2nd most common cause of irreversible vision loss in the United States. Nearly 67 million people have the disease worldwide including >3 million in the United States. A major risk factor for POAG is an elevation in intraocular pressure (IOP). The increase in IOP is believed to be caused by an increase in the deposition of extracellular matrix proteins, in particular fibronectin, in a region of the eye known as the trabecular meshwork (TM). How fibronectin contributes to the increase in IOP is not well understood. The increased density of fibronectin fibrils is thought to increase IOP by altering the compliance of the trabecular meshwork. Recent studies, however, also suggest that the composition and organization of fibronectin fibrils would affect IOP by changing the cell-matrix signaling events that control the functional properties of the cells in the trabecular meshwork. In this article, we will discuss how changes in the properties of fibronectin and fibronectin fibrils could contribute to the regulation of IOP.

Download Full-text