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Journal Francais D'ophtalmologie Sep 2020Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal... (Review)
Review
Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal angle, is the main pathway for drainage of aqueous humor (AH) out of the eye, and its dysfunction is responsible for the IOP elevation. The trabecular meshwork is a complex, fenestrated, three-dimensional structure composed of trabecular meshwork cells (TMC) interdigitated into a multilayered organization within the extracellular matrix (ECM). The purpose of this literature review is to provide an overview of current understanding of the trabecular meshwork and its pathophysiology in glaucoma. Thus, we will present the main anatomical and cellular bases for the regulation of aqueous humor outflow resistance, the pathophysiological mechanisms involved in trabecular dysfunction in the various types of glaucoma, as well as current and future therapeutic strategies targeting the trabecular meshwork.
Topics: Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Optic Nerve Diseases; Trabecular Meshwork; Trabeculectomy
PubMed: 32561029
DOI: 10.1016/j.jfo.2020.05.002 -
Biochemia Medica Oct 2020Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and a leading cause of blindness in working-age adults in... (Review)
Review
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and a leading cause of blindness in working-age adults in developed countries. Numerous investigations have recognised inflammation and angiogenesis as important factors in the development of this complication of diabetes. Current methods of DR treatment are predominantly used at advanced stages of the disease and could be associated with serious side effects. Therefore, new diagnostic methods are needed in order to identify the initial stages of DR as well as monitoring the effects of applied therapy. Biochemical biomarkers are molecules found in blood or other biological fluid and tissue that indicate the existence of an abnormal condition or disease. They could be a valuable tool in detecting early stages of DR, identifying patients most susceptible to retinopathy progression and monitoring treatment outcomes. Biomarkers related to DR can be measured in the blood, retina, vitreous, aqueous humour and recently in tears. As the retina represents a small part of total body mass, a circulating biomarker for DR needs to be highly specific. Local biomarkers are more reliable as indicators of the retinal pathology; however, obtaining a sample of aqueous humour, vitreous or retina is an invasive procedure with potential serious complications. As a non-invasive novel method, tear analysis offers a promising direction in further research for DR biomarker detection. The aim of this paper is to review systemic and local inflammatory and angiogenic biomarkers relevant to this sight threatening diabetic complication.
Topics: Aqueous Humor; Biomarkers; Chemokines; Cytokines; Diabetes Complications; Diabetic Retinopathy; Humans; Insulin-Like Growth Factor I; Tears; Vascular Endothelial Growth Factor A
PubMed: 32774120
DOI: 10.11613/BM.2020.030502 -
Experimental Eye Research Feb 2022In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs... (Review)
Review
In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs are short, single-stranded, and noncoding RNAs that regulate gene expression in a number of physiological conditions and human diseases, including glaucoma. Numerous miRNAs display differential expression in glaucoma-affected tissues, such as aqueous humor, tears, trabecular meshwork, and retina analyzed from patients and animal models, suggesting their potential involvement in glaucoma pathogenesis. Several studies summarized here have also investigated the challenge of delivering intact miRNAs to target tissues in order to develop miRNA-based glaucoma therapies. We extend these reports by conducting an additional layer of analysis that integrates the interaction between glaucoma-related miRNAs and glaucoma-associated genes. We conclude with a comprehensive discussion of the therapeutic potential of miRNAs, the cellular pathways that link these miRNAs together, and the most promising miRNAs for future glaucoma research.
Topics: Animals; Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; MicroRNAs; Trabecular Meshwork
PubMed: 34968473
DOI: 10.1016/j.exer.2021.108909 -
Proceedings of the National Academy of... Jul 2022The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential...
The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some disorders, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that compose these tissues, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq). We profiled 195,248 nuclei from nondiseased anterior segment tissues of six human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in the lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment, revealing that some cell types are unique to a single structure, whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type-specific expression patterns of more than 900 human ocular disease genes identified through either Mendelian inheritance patterns or genome-wide association studies.
Topics: Adult; Anterior Eye Segment; Aqueous Humor; Atlases as Topic; Ciliary Body; Eye Diseases; Genome-Wide Association Study; Humans; Iris; Organ Specificity
PubMed: 35858321
DOI: 10.1073/pnas.2200914119 -
Acta Ophthalmologica Jun 2022In a healthy eye, the aqueous humour (AH) flows via the ciliary body and trabecular meshwork into the collector channels, which carry it to the episcleral veins. In... (Review)
Review
In a healthy eye, the aqueous humour (AH) flows via the ciliary body and trabecular meshwork into the collector channels, which carry it to the episcleral veins. In glaucoma, a heterogeneous group of eye disorders affecting approximately 60 million individuals worldwide, the juxtacanalicular meshwork offers greater resistance to the outflow of the AH, leading to an increase in outflow resistance that gradually results in elevated intraocular pressure (IOP). The present review comprehensively covers the morphology of Schlemm's canal (SC) and AH pathways. The path of the AH from the anterior chamber through the trabeculum into suprascleral and conjunctival veins via collector channels is described, and the role of SC in the development of glaucoma and outflow resistance is discussed. Finally, channelography is presented as a precise method of assessing the conventional drainage pathway and facilitating localization of an uncollapsed collector and aqueous veins. Attention is also given to the relationship between aqueous and episcleral veins and heartbeat. Possible directions of future research are proposed.
Topics: Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Sclera; Trabecular Meshwork
PubMed: 34519170
DOI: 10.1111/aos.15027 -
Investigative Ophthalmology & Visual... Aug 2022We develop a mathematical model that predicts aqueous humor (AH) production rate by the ciliary processes and aqueous composition in the posterior chamber (PC), with the...
PURPOSE
We develop a mathematical model that predicts aqueous humor (AH) production rate by the ciliary processes and aqueous composition in the posterior chamber (PC), with the aim of estimating how the aqueous production rate depends on the controlling parameters and how it can be manipulated.
METHODS
We propose a compartmental mathematical model that considers the stromal region, ciliary epithelium, and PC. All domains contain an aqueous solution with different chemical species. We impose the concentration of all species on the stromal side and exploit the various ion channels present on the cell membrane to compute the water flux produced by osmosis, the solute concentrations in the AH and the transepithelial potential difference.
RESULTS
With a feasible set of parameters, the model predictions of water flux from the stroma to the PC and of the solute concentrations in the AH are in good agreement with measurements. Key parameters which impact the aqueous production rate are identified. A relevant role is predicted to be played by cell membrane permeability to \(\text{K}^+\) and \(\text{Cl}^-\), by the level of transport due to the Na+-H+ exchanger and to the co-transporter of Na+/K+/2Cl-; and by carbonic anhydrase.
CONCLUSIONS
The mathematical model predicts the formation and composition of AH, based on the structure of the ciliary epithelium. The model provides insight into the physical processes underlying the functioning of drugs that are adopted to regulate the aqueous production. It also suggests ion channels and cell membrane properties that may be targeted to manipulate the aqueous production rate.
Topics: Aqueous Humor; Ciliary Body; Ion Channels; Models, Theoretical; Water
PubMed: 35917134
DOI: 10.1167/iovs.63.9.1 -
Survey of Ophthalmology 2022The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and... (Review)
Review
The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and uveal tissues were historically considered "alymphatic" and thought to be immune privileged. The very fact that the aqueous outflow channels carry a clear fluid (aqueous humor) along the outflow pathway makes it hard to ignore its lymphatic-like characteristics. The development of novel lymphatic lineage markers and expression of these markers in aqueous outflow channels and improved imaging capabilities has sparked a renewed interest in the study of ocular lymphatics. Ophthalmic lymphatic research has had a directional shift over the last decade, offering an exciting new physiological platform that needs further in-depth understanding. The evidence of a presence of distinct lymphatic channels in the human ciliary body is gaining significant traction. The uveolymphatic pathway is an alternative new route for aqueous outflow and adds a new dimension to pathophysiology and management of glaucoma. Developing novel animal models, markers, and non-invasive imaging tools to delineate the core anatomical structure and physiological functions may help pave some crucial pathways to understand disease pathophysiology and help develop novel targeted therapeutic approaches for glaucoma.
Topics: Animals; Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Lymphatic Vessels; Sclera; Trabecular Meshwork; Uvea
PubMed: 34656556
DOI: 10.1016/j.survophthal.2021.10.004 -
Experimental Eye Research May 2017Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of... (Review)
Review
Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or 'unconventional' route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans.
Topics: Animals; Aqueous Humor; Humans; Intraocular Pressure; Limbus Corneae; Models, Animal; Sclera; Secretory Pathway; Trabecular Meshwork; Uvea
PubMed: 26850315
DOI: 10.1016/j.exer.2016.01.017 -
BMC Ophthalmology Aug 2023To explore differential metabolites in the aqueous humor of patients with different axial lengths and their correlations with axial length and choroidal parameters.
BACKGROUND
To explore differential metabolites in the aqueous humor of patients with different axial lengths and their correlations with axial length and choroidal parameters.
METHODS
In this study, we included 12 patients with axial lengths less than 24 mm, 11 patients with axial lengths between 24 and 26 mm, and 11 patients with axial lengths greater than 26 mm. We collected their aqueous humor samples during cataract surgery for liquid chromatography-mass spectrometry metabolomic analysis. Simultaneously, we collected relevant clinical parameters such as axial length, subfoveal choroidal thickness, and choroidal vascular index. Correlations between clinical data, differential metabolites, and clinical indicators were analyzed. In addition, we plotted receiver operating characteristic curves.
RESULTS
The results showed that axial length was significantly negatively correlated with choroidal thickness (r=-0.7446, P < 0.0001), and that several differential metabolites were significantly correlated with certain clinical parameters. After analyzing receiver operating characteristic curves, 5-methoxytryptophol and cerulenin were found to have excellent discriminative power, demonstrating their potential as biomarkers. In the enrichment analysis, we found that the differential metabolites among each group were involved in several special pathways (Taurine and Hypotaurine Metabolism, Vitamin B6 Metabolism, Pantothenate, and coenzyme A Biosynthesis), suggesting that abnormalities in these metabolic pathways may play a role in the process of axial myopia.
CONCLUSIONS
Our study identified alterations in certain metabolic pathways in different axial lengths. At the same time, we found several metabolites with significant correlation with clinical indicators, among which 5-methoxytryptophol and cerulenin were associated with axial myopia.
CLINICAL TRIAL REGISTRATION
Registration date:11/04/2022.
TRIAL REGISTRATION NUMBER
ChiCTR2200058575.
TRIAL REGISTRY
The First Affiliated Hospital of the Zhejiang University School of Medicine.
Topics: Humans; Aqueous Humor; Cerulenin; Myopia; Metabolomics; Choroid; Axial Length, Eye; Tomography, Optical Coherence
PubMed: 37582698
DOI: 10.1186/s12886-023-03101-1 -
Investigative Ophthalmology & Visual... May 2015
Review
Topics: Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Trabecular Meshwork
PubMed: 26024085
DOI: 10.1167/iovs.15-16744