The Pathophysiology and Treatment of Glaucoma

JAMA, Journal Year: 2014, Volume and Issue: 311(18), P. 1901 - 1901

Published: May 13, 2014

Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until relatively late stage, diagnosis frequently delayed. A general understanding the disease pathophysiology, diagnosis, and treatment assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination more actively participating affected by this condition.To describe current evidence regarding pathophysiology open-angle glaucoma angle-closure glaucoma.A literature search was conducted using MEDLINE, Cochrane Library, manuscript references studies published English between January 2000 September 2013 on topics glaucoma. From 4334 abstracts screened, 210 articles were selected that contained information with relevance to physicians.The glaucomas are group progressive optic neuropathies characterized degeneration retinal ganglion cells resulting changes nerve head. Loss related level intraocular pressure, but other factors also play role. Reduction pressure only proven method treat disease. Although usually initiated ocular hypotensive drops, laser trabeculoplasty surgery used slow progression.Primary can an important role positive family history or suspicious head findings complete examination. They improve outcomes reinforcing importance medication adherence persistence recognizing adverse reactions from medications surgeries.

Language: Английский

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The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease

Cell, Journal Year: 2020, Volume and Issue: 182(2), P. 270 - 296

Published: July 1, 2020

Language: Английский

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Inflammation in Glaucoma: From the back to the front of the eye, and beyond

Progress in Retinal and Eye Research, Journal Year: 2020, Volume and Issue: 83, P. 100916 - 100916

Published: Oct. 17, 2020

The pathophysiology of glaucoma is complex, multifactorial and not completely understood. Elevated intraocular pressure (IOP) and/or impaired retinal blood flow may cause initial optic nerve damage. In addition, age-related oxidative stress in the retina concurrently with chronic mechanical vascular crucial for initiation neurodegeneration. Oxidative closely related to cell senescence, mitochondrial dysfunction, excitotoxicity, neuroinflammation, which are involved progression. Accumulating evidence from animal models human ocular samples suggests a dysfunction para-inflammation ganglion layer head. Moreover, quite similar mechanisms anterior chamber could explain trabecular meshwork elevated IOP primary open-angle glaucoma. On other hand, surface disease due topical interventions most prominent visible consequence inflammation glaucoma, negative impact on filtering surgery failure, treatment efficacy, possibly segment. Consequently, appears as an outstanding eye where inflammatory changes be present various extents consequences along structure, posterior segment, visual pathway. Here we reviewed processes all structures back front beyond. Our approach was how necessary maintain homoeostasis, describe abnormal findings observed glaucomatous patients or models, supporting hypothesis dysregulation balance toward pro-inflammatory phenotype. Possible anti-inflammatory therapeutic approaches also discussed.

Language: Английский

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Researching glutamate – induced cytotoxicity in different cell lines: a comparative/collective analysis/study

Frontiers in Cellular Neuroscience, Journal Year: 2015, Volume and Issue: 9

Published: March 17, 2015

Although glutamate is one of the most important excitatory neurotransmitters central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization neurons, a toxic process called, excitotoxicity. In excitotoxicity triggers rise intracellular Ca2+ influx, followed by up regulation nNOS, dysfunction mitochondria, ROS production, ER stress and release lysosomal enzymes. Excessive calcium key mediator toxicity through over activation ionotropic metabotropic receptors. addition, accumulation can also inhibit cystine uptake reversing action cystine/glutamate antiporter. Reversal antiporter reinforces aforementioned events depleting neurons cysteine eventually glutathione's reducing potential. Various cell lines have been employed in pursuit understand mechanism(s) which affects cells leading them ultimately their demise. some exerted mainly NMDA, AMPA or Kainate receptors whereas other lacking such receptors, due induced oxidative stress. However greatest majority ionotropic-glutamate are present, co-existing antiporters supporting assumption that effect these accumulative. Different differ responses when exposed glutamate. this review article PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical RGC-5 SCN2.2 systems systematically collected analyzed.

Language: Английский

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Retinal remodeling in human retinitis pigmentosa

Experimental Eye Research, Journal Year: 2016, Volume and Issue: 150, P. 149 - 165

Published: March 26, 2016

Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt function or architecture of photoreceptors. While RP can initially be photoreceptors, there increasing evidence inner retina becomes progressively disorganized as outer degenerates. These alterations have been extensively described animal models, but remodeling humans has not well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding retinal process humans. We describe cone mediated preservation overall topology, reprogramming earliest stages bipolar cells, and both small molecule protein signatures neurons glia. Furthermore, while Müller glia appear some last cells left degenerate retina, they are also one first cell classes respond stress which may reveal mechanisms related death other classes. Also fundamentally important finding network topologies altered. Our results suggest interventions presume substantial will likely fail late disease. Even early intervention offers no guarantee immune progressive remodeling. Fundamental work biology progression needed support vision rescue strategies.

Language: Английский

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Critical pathogenic events underlying progression of neurodegeneration in glaucoma

Progress in Retinal and Eye Research, Journal Year: 2012, Volume and Issue: 31(6), P. 702 - 719

Published: Aug. 1, 2012

Language: Английский

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LncRNA H19 initiates microglial pyroptosis and neuronal death in retinal ischemia/reperfusion injury

Cell Death and Differentiation, Journal Year: 2019, Volume and Issue: 27(1), P. 176 - 191

Published: May 24, 2019

Abstract Ischemia-reperfusion (I/R) is a common pathology when the blood supply to an organ was disrupted and then restored. During reperfusion process, inflammation tissue injury were triggered, which mediated by immunocytes cytokines. However, mechanisms initiating I/R-induced driving activation remained largely unknown. In this study, we identified long non-coding RNA (lncRNA)-H19 as key onset of inflammation. We found that I/R increased lncRNA-H19 expression significantly promote NLRP3/6 inflammasome imbalance resulted in microglial pyroptosis, cytokines overproduction, neuronal death. These damages effectively inhibited knockout. Specifically, functioned via sponging miR-21 facilitate PDCD4 formed competing endogenous network (ceRNET) ischemic cascade. LncRNA H19/miR-21/PDCD4 ceRNET can directly regulate sterile lesion vivo. thus propose previously unknown danger signals molecular immunological pathways injury, pharmacological approaches inhibit H19 seem likely become treatment modalities for patients near future based on these mechanistic findings.

Language: Английский

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Autophagy in the eye: Development, degeneration, and aging

Progress in Retinal and Eye Research, Journal Year: 2016, Volume and Issue: 55, P. 206 - 245

Published: Aug. 25, 2016

Language: Английский

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The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel

Journal of Clinical Investigation, Journal Year: 2014, Volume and Issue: 124(9), P. 3975 - 3986

Published: July 24, 2014

In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with lymphatic vascular system, it unknown whether SC a blood or vessel. Here, we demonstrated expression of endothelial cell markers by in murine zebrafish models as well human eye tissue. The initial stages development involved induction transcription factor PROX1 lymphangiogenic receptor tyrosine kinase VEGFR-3 venous cells postnatal mice. Using gene deletion function-blocking antibodies mice, determined that growth VEGF-C its receptor, VEGFR-3, are essential for development. Delivery adult resulted sprouting, proliferation, cells, whereas VEGF-A obliterated system. Furthermore, single injection recombinant induced was associated trend toward sustained decrease intraocular pressure These results reveal evolutionary conservation lymphatic-like phenotype SC, implicate critical regulators lymphangiogenesis, provide basis further studies on therapeutic manipulation glaucoma treatment.

Language: Английский

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The Aging Eye: Common Degenerative Mechanisms Between the Alzheimer's Brain and Retinal Disease

Investigative Ophthalmology & Visual Science, Journal Year: 2013, Volume and Issue: 54(1), P. 871 - 871

Published: Jan. 30, 2013

Alzheimer's disease (AD) is a common, incurable, and progressive dementia, characterized by loss of learning memory the neuropathologic accumulation amyloid plaques neurofibrillary tangles in brain. A number similarities between AD pathology several distinct retinal degenerations have been described, particularly with respect to either glaucoma or age-related macular degeneration (AMD), each leading cause vision blindness worldwide. Although comparisons these diseases may provide important new insights into their pathogenic mechanisms, AMD result markedly different degenerations. Therefore, analyses differences conditions prove equally productive. Common mechanisms that appear underlie all three are explored here, as well potential use retina biomarker for diagnosis progression. Based on this comparison, past current efforts transfer therapeutic strategies discussed.

Language: Английский

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