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The Journal of Physiological Sciences :... Mar 2024Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits... (Review)
Review
Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits through the trabecular meshwork (TM). IOP follows a circadian rhythm synchronized with the suprachiasmatic nucleus (SCN), the circadian pacemaker. The SCN resets peripheral clocks through sympathetic nerves or adrenal glucocorticoids (GCs). IOP's circadian rhythm is governed by circadian time signals, sympathetic noradrenaline (NE), and GCs, rather than the local clock. The activity of Na/K-ATPase in non-pigmented epithelial cells in the ciliary body can influence the nocturnal increase in IOP by enhancing AH inflow. Conversely, NE, not GCs, can regulate the IOP rhythm by suppressing TM macrophage phagocytosis and AH outflow. The activation of the β1-adrenergic receptor (AR)-mediated EPAC-SHIP1 signal through the ablation of phosphatidylinositol triphosphate may govern phagocytic cup formation. These findings could offer insights for better glaucoma management, such as chronotherapy.
Topics: Humans; Intraocular Pressure; Glaucoma; Trabecular Meshwork; Aqueous Humor; Circadian Rhythm; Glucocorticoids
PubMed: 38431563
DOI: 10.1186/s12576-024-00905-8 -
BMC Ophthalmology Jan 2020Serum 25-hydroxyvitamin D (25 (OH) D) levels are associated with various pathologic ocular conditions. Few studies have assessed 25 (OH) D concentrations in non-serum...
BACKGROUND
Serum 25-hydroxyvitamin D (25 (OH) D) levels are associated with various pathologic ocular conditions. Few studies have assessed 25 (OH) D concentrations in non-serum specimens, and none to date has assessed 25 (OH) D concentrations in human aqueous humor and their association with ocular diseases. This study investigated the possible correlations between 25 (OH) D concentrations in aqueous humor and serum and whether vitamin D concentrations in aqueous humor were associated with cataract.
METHODS
This study prospectively enrolled 136 patients, including 87 with senile cataract and 49 with diabetic cataract, who underwent cataract surgery from January to November 2017. 25 (OH) D was measured in aqueous humor and serum specimens collected from all patients, and their correlation was analyzed statistically. Clinical and laboratory data, including the results of ophthalmologic examinations, were compared in the two groups of cataract patients.
RESULTS
No correlation was observed between 25 (OH) D concentrations in aqueous humor and serum (P = 0.381). 25 (OH) D concentrations in aqueous humor were significantly higher in patients with diabetic than senile cataract (P = 0.006). Multivariate logistic regression analysis showed that the adjusted odds ratio for diabetic cataract for the highest compared with the lowest quartile of 25 (OH) D concentration in aqueous humor was 4.36 ng/ml (95% confidence interval [CI]: 1.33-14.34 ng/ml; P = 0.015). Multivariate linear regression analysis showed that 25(OH) D concentration in aqueous humor was 2.68 ng/ml (95% CI: 0.34-5.01 ng/ml; P = 0.025) higher in patients with diabetic than senile cataract.
CONCLUSIONS
25(OH) D concentrations in aqueous humor and serum did not correlate with each other. Higher 25(OH) D level in aqueous humor was associated with diabetic cataract. These findings suggest that studies of vitamin D levels in patients with ocular conditions should include measurements of vitamin D levels in aqueous humor.
Topics: Aged; Aged, 80 and over; Aqueous Humor; Cataract; Female; Humans; Male; Middle Aged; Prospective Studies; Regression Analysis; Vitamin D
PubMed: 31906919
DOI: 10.1186/s12886-019-1293-9 -
Molecular & Cellular Proteomics : MCP 2021Glaucoma is the leading cause of irreversible blindness worldwide. The proteome characterization of glaucoma is not clearly understood. A total of 175 subjects,...
Glaucoma is the leading cause of irreversible blindness worldwide. The proteome characterization of glaucoma is not clearly understood. A total of 175 subjects, including 57 primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patients, were enrolled and comparison proteomic analysis was provided. The samples were randomly divided into discovery group or validation group, whose aqueous humor proteome was analyzed by data-independent acquisition or by parallel reaction monitoring. The common proteome features of three types of glaucoma were immune response, lipid metabolism, and cell death. Three proteins, VTN, SERPIND1, and CD14, showed significant upregulation in glaucoma and could discriminate glaucoma from cataract. Mutual differential proteomic analysis of PAACG, PCACG, and NVG showed different proteome characterization of the three types of glaucoma. NVG was characterized with activated angiogenesis. PAACG was characterized with activation of inflammation response. SERPIND1 was discovered to play vital role in glaucoma occurrences, which is associated with eye transparency decrease and glucose metabolism. This study would provide insights in understanding proteome characterization of glaucoma and benefit the clinical application of AH proteome.
Topics: Aged; Aged, 80 and over; Aqueous Humor; Cataract; Female; Glaucoma; Humans; Male; Middle Aged; Proteome
PubMed: 34214668
DOI: 10.1016/j.mcpro.2021.100117 -
PloS One 2022To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated...
To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.
Topics: Aqueous Humor
PubMed: 35061677
DOI: 10.1371/journal.pone.0254972 -
Cellular and Molecular Life Sciences :... Sep 2022The ciliary body critically contributes to the ocular physiology with multiple responsibilities in the production of aqueous humor, vision accommodation and intraocular...
The ciliary body critically contributes to the ocular physiology with multiple responsibilities in the production of aqueous humor, vision accommodation and intraocular immunity. Comparatively little work, however, has revealed the single-cell molecular taxonomy of the human ciliary body required for studying these functionalities. In this study, we report a comprehensive atlas of the cellular and molecular components of human ciliary body as well as their interactions using single-cell RNA sequencing (scRNAseq). Cluster analysis of the transcriptome of 14,563 individual ciliary cells from the eyes of 3 human donors identified 14 distinct cell types, including the ciliary epithelium, smooth muscle, vascular endothelial cell, immune cell and other stromal cell populations. Cell-type discriminative gene markers were also revealed. Unique gene expression patterns essential for ciliary epithelium-mediated aqueous humor inflow and ciliary smooth muscle contractility were identified. Importantly, we discovered the transitional states that probably contribute to the transition of ciliary macrophage into retina microglia and verified no lymphatics in the ciliary body. Moreover, the utilization of CellPhoneDB allowed us to systemically infer cell-cell interactions among diverse ciliary cells including those that potentially participate in the pathogenesis of glaucoma and uveitis. Altogether, these new findings provide insights into the regulation of intraocular pressure, accommodation reflex and immune homeostasis under physiological and pathological conditions.
Topics: Aqueous Humor; Ciliary Body; Glaucoma; Humans; Intraocular Pressure; Transcriptome
PubMed: 36163311
DOI: 10.1007/s00018-022-04559-w -
Molecular Vision 2015The etiology of keratoconus (KC) and the factors governing its progression are not well understood. It has been suggested that this disease might be caused by...
PURPOSE
The etiology of keratoconus (KC) and the factors governing its progression are not well understood. It has been suggested that this disease might be caused by biochemical alterations in the cornea; changes in the expression profiles of human aqueous humor (hAH) proteins have been observed in some diseases. To gain a new insight into the molecular mechanisms of KC pathology, we examined the hAH proteomes of those in the advanced stages of this disease. We used a high-throughput mass spectrometry approach to compare hAH protein expression in patients with KC and in control subjects.
METHODS
Aqueous humor samples were acquired from five keratoconus patients during keratoplasty surgery and from five myopic control subjects during phakic intraocular lens implantation. Quantitative mass spectrometry analysis using spectral counting was performed to determine the relative amounts of hAH proteins in the samples from KC patients and control individuals.
RESULTS
All KC patients included in the study presented severe keratoconus (K2 >52 D), and slit-lamp examination revealed microfolds in Descemet's membrane, without clinical signs of hydrops. We found significant differences between the expression levels of 16 proteins in the two groups. In KC samples, seven proteins were overexpressed and nine were underexpressed in comparison with the control group. Gene ontology analysis revealed that these deregulated proteins are implicated in several biologic processes, such as the regulation of proteolysis, responses to hypoxia, and responses to hydrogen peroxide, among others.
CONCLUSIONS
The protein expression profiles in hAH from KC patients and myopic control subjects differ significantly. This result suggests that some components of the hAH proteome are involved in this disease. Further in-depth analysis of the hAH proteome should provide a better understanding of the mechanisms governing the pathophysiology of KC.
Topics: Adult; Aqueous Humor; Case-Control Studies; Chromatography, Liquid; Down-Regulation; Eye Proteins; Female; Gene Ontology; Humans; Keratoconus; Male; Protein Interaction Maps; Proteomics; Reference Values; Tandem Mass Spectrometry; Up-Regulation
PubMed: 25999673
DOI: No ID Found -
Eye (London, England) Jan 2021Elevated intraocular pressure (IOP) is the primary risk factor for blindness in glaucoma. IOP is determined by many factors including aqueous humour production and... (Review)
Review
Elevated intraocular pressure (IOP) is the primary risk factor for blindness in glaucoma. IOP is determined by many factors including aqueous humour production and aqueous humour outflow (AHO), where AHO disturbance represents the primary cause of increased IOP. With the recent development of new IOP lowering drugs and Minimally Invasive Glaucoma Surgeries (MIGS), renewed interest has arisen in shedding light on not only how but where AHO is occurring for the trabecular/conventional, uveoscleral/unconventional, and subconjunctival outflow pathways. Historical studies critical to understanding outflow anatomy will be presented, leading to the development of modern imaging methods. New biological behaviours uncovered by modern imaging methods will be discussed with relevance to glaucoma therapies emphasized.
Topics: Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Minimally Invasive Surgical Procedures
PubMed: 33060830
DOI: 10.1038/s41433-020-01215-0 -
Experimental Eye Research Aug 2022The distal outflow pathway of the human eye consists of the outer wall of Schlemm's canal, collector channels, and the deep-scleral, mid-scleral and episcleral vessels.... (Review)
Review
The distal outflow pathway of the human eye consists of the outer wall of Schlemm's canal, collector channels, and the deep-scleral, mid-scleral and episcleral vessels. It is the last region of transit for aqueous humor before returning to the venous system. While the trabecular meshwork, scleral spur, and inner wall of Schlemm's canal have been extensively analyzed to define their contributions to aqueous outflow, the role of the distal outflow pathway is not completely understood. Collector channels, emanating from Schlemm's canal were previously thought to be passive conduits for aqueous humor. However, recent studies have shown many collector channels contain flap-like appendages which move with changes in pressure. These findings, along with studies demonstrating innervation of episcleral vessels, have led to questions regarding whether other structures in the distal outflow pathway are under neural regulation and how this may influence aqueous humor outflow. This study evaluates the innervation of the outer wall of Schlemm's canal and collector channels, along with the deep-scleral, mid-scleral and episcleral vasculature with microcomputed tomography and 3-dimensional reconstruction, correlative light microscopy, immunohistochemistry, and transmission electron microscopy. Peripheral, autonomic, and sensory nerve fibers were found to be present adjacent to Schlemm's canal outer wall endothelium, collector channel endothelium, and in the different regions of the distal outflow vasculature. Nerves were more commonly identified in regions that contained collector channels when compared to regions without collector channels. These findings regarding the neural anatomy suggest an active neural regulation of aqueous humor outflow throughout the proximal and distal regions of the conventional outflow pathway.
Topics: Aqueous Humor; Humans; Intraocular Pressure; Microscopy, Electron, Transmission; Sclera; Trabecular Meshwork; X-Ray Microtomography
PubMed: 35636488
DOI: 10.1016/j.exer.2022.109132 -
Advances in Clinical and Experimental... Sep 2021The pathogenesis of myopia remains unclear. Both genetic and environmental factors play a role in the disease progression. Reasons including reduced physical activity...
BACKGROUND
The pathogenesis of myopia remains unclear. Both genetic and environmental factors play a role in the disease progression. Reasons including reduced physical activity (PA) and low-grade intraocular inflammation may be involved in the development of myopia.
OBJECTIVES
To analyze the levels of irisin, brain-derived neurotrophic factor (BDNF) and other intraocular cytokines in aqueous humor of high myopia patients, and to evaluate the roles of PA and inflammation in developing myopia.
MATERIAL AND METHODS
We collected aqueous humor samples from patients with axial length (AL) over 26 mm (n = 35) or shorter than 25 mm (n = 38) during cataract extraction surgery. Samples were assayed using the enzyme-linked immunosorbent assay (ELISA) kit for irisin and a multiplex immunoassay kit for BDNF, interleukin (IL)-6, IL-8 and IL-10, and tumor necrosis factor alpha (TNF-α).
RESULTS
Irisin levels in the aqueous samples of the highly myopic eyes were significantly higher than in the control group (p = 0.027). The BDNF levels of the highly myopic group were significantly lower than in the control group (p = 0.043). Median level of leukemia inhibitory factor (LIF) for highly myopic group (2.035 pg/mL) was statistically significantly higher than in the control group (0.750 pg/mL) (U = 210.5, Z = -4.495, p < 0.001). Interleukin 1 receptor antagonist (IL-1ra) level in the aqueous samples of the highly myopic group was significantly lower than in the shorter AL group (p = 0.049). Interleukin 6, IL-8 and IL-10 levels were not significantly different between the 2 groups (p = 0.501, p = 0.059 and p = 0.192, respectively). Tumor necrosis factor α levels could only be detected in 30 samples and median levels in the 2 groups were not statistically significantly different (U = 99, Z = -0.482, p = 0.650). No correlation was found between IL-6, IL-8, IL-10 and TNF-α, and the AL (p > 0.05). Irisin was positively correlated with AL (p = 0.028, r = 0.287). The BDNF was negatively correlated with AL (p = 0.040, r = -0.246). Interleukin 1ra was negatively correlated with AL (p = 0.038, r = -0.276). There was also a correlation between LIF and AL (p < 0.001, r = 0.486).
CONCLUSIONS
Higher irisin level in high myopia group opens a new direction to discover the relationship between PA and myopia. The decreased BDNF in high myopia group probably demonstrates the connection between myopia and neurodegenerative disease.
Topics: Aqueous Humor; Brain-Derived Neurotrophic Factor; Cytokines; Fibronectins; Humans; Myopia
PubMed: 34160912
DOI: 10.17219/acem/125428 -
Journal of Cataract and Refractive... Aug 2014The elevated intraocular pressure (IOP) of primary open-angle glaucoma is caused by impaired outflow of aqueous humor through the trabecular meshwork. Within the... (Review)
Review
UNLABELLED
The elevated intraocular pressure (IOP) of primary open-angle glaucoma is caused by impaired outflow of aqueous humor through the trabecular meshwork. Within the juxtacanalicular region, alterations of both extracellular matrix homeostasis and the cellular tone of trabecular meshwork endothelial and the inner wall of Schlemm canal cells affect outflow. Newer pharmacologic agents that target trabecular meshwork and Schlemm canal cell cytoskeleton lower IOP. Aqueous drainage occurs nonhomogenously with greater flow going through certain portions of the TM and less going through other portions-a concept known as segmental flow, which is theoretically the result of outflow being dependent on the presence of discrete pores within Schlemm canal. The limited long-term success of trabecular meshwork bypass surgeries implicates the potential impact of resistance in Schlemm canal itself and collector channels. Additionally, others have observed that outflow occurs preferentially near collector channels. These distal structures may be more important to aqueous outflow than previously believed.
FINANCIAL DISCLOSURE
Dr. Rhee is a consultant to Aerie Pharmaceuticals, Alcon Laboratories, Inc., Allegan, Inc., Aquesys, Inc., Glaukos Corp., Ivantis, Inc., Johnson & Johnson, Merck Sharp & Dohme Corp. and Santen, Inc., and has received research funding from Alcon Laboratories, Inc., Merck Sharp & Dohme Corp., and Ivantis, Inc. No other author has a financial or proprietary interest in any material or method mentioned.
Topics: Antihypertensive Agents; Aqueous Humor; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Trabecular Meshwork
PubMed: 25088623
DOI: 10.1016/j.jcrs.2014.06.020