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PloS One 2023Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes mellitus, and inflammatory pathways have been linked to its pathogenesis. In this... (Observational Study)
Observational Study
Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes mellitus, and inflammatory pathways have been linked to its pathogenesis. In this retrospective, observational pilot study, we aimed to compare the concentrations of four inflammation-related proteins, ZAG, Reg-3a, elafin and RBP-4, in the serum and aqueous humor of healthy controls and diabetic patients with different stages of DR. The concentrations of VEGF-A, IL-8, IL-6 were determined in parallel as internal controls. In the serum, we did not find significant differences in the concentrations of target proteins. In the aqueous humor, higher levels of ZAG, RBP-4, Reg-3a and elafin were observed in advanced nonproliferative DR (NPDR)/ proliferative DR (PDR) compared to controls. The levels of ZAG and RBP-4 were also higher in advanced NPDR/PDR than in nonapparent DR. Normalization of target protein concentrations to the aqueous humor total protein demonstrates that a spill-over from serum due to breakage of the blood-retina barrier only partially accounts for increased inflammation related markers in later stages. In conclusion, we found elevated levels of Reg-3a, RBP-4, elafin and ZAG in advanced stages of diabetic retinopathy. Higher levels of pro-inflammatory proteins, Reg-3a and RBP-4, might contribute to the pathogenesis of diabetic retinopathy, as the parallel increased concentrations of anti-inflammatory molecules elafin and ZAG might indicate a compensatory mechanism.
Topics: Humans; Diabetic Retinopathy; Elafin; Retrospective Studies; Aqueous Humor; Inflammation; Diabetes Mellitus, Type 2
PubMed: 37883447
DOI: 10.1371/journal.pone.0293139 -
Experimental Eye Research Aug 2020We reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology... (Review)
Review
BACKGROUND
We reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology of POAG.
METHODS
We searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG (cases) and cataract (controls). Untargeted studies (measuring the whole proteome, by LC-MS/MS) were divided into two subgroups depending on the type of surgery during which POAG AH was collected: glaucoma filtration surgery (subgroup 1) or cataract surgery (subgroup 2). We reanalyzed the raw data (subgroup 1) or combined the reported data (subgroup 2) to perform GO enrichment (GOrilla) and pathway analysis (Pathvisio).
RESULTS
Out of 93 eligible proteomic studies, seven were untargeted studies that identified 863 AH proteins. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2. Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. For subgroup 1 but not for subgroup 2, proteins of the complement system were significantly enriched.
CONCLUSION
AH proteome of POAG patients shows strong activation of the immune system. In addition, analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors. In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression.
Topics: Aqueous Humor; Eye Proteins; Glaucoma, Open-Angle; Humans; Protein Processing, Post-Translational; Proteome
PubMed: 32470343
DOI: 10.1016/j.exer.2020.108077 -
BMC Ophthalmology Oct 2016To study the value and safety of aqueous humor polymerase chain reaction (PCR) analysis for Herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus and...
BACKGROUND
To study the value and safety of aqueous humor polymerase chain reaction (PCR) analysis for Herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus and Toxoplasma gondii in patients with uveitis.
METHODS
Records of 45 consecutive patients with anterior and posterior uveitis who underwent AC paracentesis with PCR were reviewed. The main outcome measure was frequency of PCR positivity. Secondary outcomes were alteration of treatment, safety of paracentesis, and correlation of keratitic precipitates with PCR positivity, RESULTS: The overall PCR positivity was 48.9 % (22/45). Therapy was changed because of the PCR results in 14/45 patients (37.7 %). One patient experienced a paracentesis related complication (1/45, 2.2 %) without long-term sequelae.
CONCLUSION
Aqueous PCR altered the diagnosis and treatment in over a third of our patients and was relatively safe. Aqueous PCR should be considered for uveitis of atypical clinical appearance, recurrent severe uveitis of uncertain etiology, and therapy refractory cases.
Topics: Adult; Aged; Aqueous Humor; Diagnostic Techniques, Ophthalmological; Eye Infections, Viral; Female; Humans; Male; Middle Aged; Polymerase Chain Reaction; Toxoplasmosis; Uveitis; Young Adult
PubMed: 27793120
DOI: 10.1186/s12886-016-0369-z -
Transactions of the American... Dec 2011To use an integrated proteohistologic approach to gain insight into the anterior segment alterations in the buphthalmic rabbit. (Review)
Review
PURPOSE
To use an integrated proteohistologic approach to gain insight into the anterior segment alterations in the buphthalmic rabbit.
METHODS
Eyes from 2- and 5-year-old buphthalmic and normal rabbits (n=20) were studied histologically. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of aqueous humor (AH) was used to determine differential protein expression between animal groups. Western blot and immunohistochemistry were performed on selected differentially expressed proteins identified by LC-MS/MS.
RESULTS
The buphthalmic rabbits manifested a mild clinical phenotype with typical angle anomalies that appeared progressive by histology. Significantly thickened Descemet's membrane (DM) and anterior lens capsule in all buphthalmic rabbits showed increased fibronectin and collagen-IV immunolabeling. LC-MS/MS applying stringent filtering criteria revealed significant differential expression of several AH proteins in these rabbits. The protein of interest in the 2-year-old group was histidine-rich glycoprotein, and those in the 5-year-old group included alpha-2-HS-glycoprotein, clusterin, apolipoprotein E, interphotoreceptor retinoid-binding protein, transthyretin, cochlin, gelsolin, haptoglobin, hemopexin, and beta-2 microglobulin. The proteomic data for selected proteins was validated by Western blot and immunohistochemistry. A wide range of functional groups were affected by the altered AH proteins. These included extracellular matrix modulation, regulation of apoptosis, oxidative stress, and protein transport.
CONCLUSIONS
Multiple anterior segment alterations were histologically identified in the buphthalmic rabbits that showed progressive changes with age. The differentially expressed AH proteins in these rabbits suggest a multifunctional role for AH in modulating pathologic changes in DM, anterior lens capsule, and the angular meshwork in these animals.
Topics: Animals; Anterior Eye Segment; Aqueous Humor; Blotting, Western; Case-Control Studies; Chromatography, Liquid; Disease Models, Animal; Eye Proteins; Hydrophthalmos; Intraocular Pressure; Proteome; Proteomics; Rabbits; Tandem Mass Spectrometry
PubMed: 22253484
DOI: No ID Found -
Cellular Physiology and Biochemistry :... 2011Glaucoma afflicts millions of people worldwide and is a major cause of blindness. The risk to develop glaucoma is enhanced by increases in IOP, which result from... (Review)
Review
Glaucoma afflicts millions of people worldwide and is a major cause of blindness. The risk to develop glaucoma is enhanced by increases in IOP, which result from deranged flow of aqueous humor. Aqueous humor is a fluid located in the front of the eye that gives the eye its buoyancy and supplies nutrients to other eye tissues. Aqueous humor is secreted by a tissue called ciliary processes and exits the eye via two tissues; the trabecular meshwork (TM) and Schlemm's canal. Because the spaces through which the fluid flows get smaller as the TM joins the area of the Schlemm's canal, there is resistance to aqueous humor outflow and this resistance creates IOP. There is a correlation between changes in TM and Schlemm's canal cell volume and rates of aqueous humor outflow; agents that decrease TM and Schlemm's canal cell volume, increase the rate of aqueous humor outflow, thus decreasing IOP. IOP is regulated by guanylate cyclase activators as shown in humans, rabbits and monkeys. There are two distinct groups of guanylate cyclases, membrane guanylate cyclase and soluble guanylate cyclase (sGC); activation of both have been shown to decrease IOP. Members of the membrane guanylate cyclase family of receptors bind to peptide ligands, while the sGC responds to gases (such as NO and CO(2)) and compounds (such as YC1, [3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole), a benzyl indazole derivative, and BAY-58-2667); activation of either results in formation of cyclic GMP (cGMP) and activation of protein kinase G (PKG) and subsequent phosphorylation of target proteins, including the high conductance calcium activated potassium channel (BKca channel). While activators of both membrane guanylate cyclase and sGC have the ability to lower IOP, the IOP lowering effects of sGC are noteworthy because sGC activators can be topically applied to the eye to achieve an effect. We have demonstrated that activators of sGC increase the rate at which aqueous humor exits the eye in a time course that correlates with the time course for sGC-induced decreases in TM and Schlemm's canal cell volume. Additionally, sGC-induced decrease in cell volume is accompanied by both K(+) and Cl(-) efflux induced by activation of K(+) and Cl(-) channels, including the BKca channel and/or K(+)Cl(-) symport. This suggests that parallel K(+)Cl(-) efflux, and resultant H(2)O efflux result in decreases in cell volume. These observations suggest a functional role for sGC activators, and suggest that the sGC/cGMP/PKG systems are potential therapeutic targets in the treatment of glaucoma.
Topics: Animals; Aqueous Humor; Cell Size; Cyclic GMP-Dependent Protein Kinases; Glaucoma; Guanylate Cyclase; Intraocular Pressure; Nitric Oxide; Trabecular Meshwork
PubMed: 22179003
DOI: 10.1159/000335866 -
Disease Markers 2021To evaluate the correlations between the inflammatory factors in the aqueous humor and hyperreflective foci (HRF) in patients with intractable macular edema treated with...
Association between Inflammatory Factors in the Aqueous Humor and Hyperreflective Foci in Patients with Intractable Macular Edema Treated with Antivascular Endothelial Growth Factor.
BACKGROUND
To evaluate the correlations between the inflammatory factors in the aqueous humor and hyperreflective foci (HRF) in patients with intractable macular edema treated with antivascular endothelial growth factor (anti-VEGF).
METHODS
This study included 17 patients with intractable macular edema (ME) treated with anti-VEGF agents. Inflammatory factors in the aqueous humor were measured by the Cytometric Beads Array before injection, and the numbers of HRF pre- and post-anti-VEGF treatment were counted from four different directions (90 degrees, 45 degrees, 180 degrees, and 135 degrees) in the SD-OCT images, respectively, before treatment and one month after treatment. The correlations between inflammatory factors and the numbers of HRF were assessed.
RESULTS
The numbers of HRF were reduced significantly after anti-VEGF treatment. The change in the HRFs at the 90-degree location was significantly positively correlated with IL-8 and VCAM-1. The change of all HRFs was significantly positively correlated with IL-8. The HRFs before the treatment also had a positive correlation with IL-8 and VCAM-1.
CONCLUSION
After anti-VEGF treatment, the numbers of HRF in intractable ME declined greatly. The higher the levels of IL-8 and VCAM-1 before treatment, the more significant the reduction of HRF after anti-VEGF treatment, which indicated that HRF could be an effective noninvasive imaging indicator for evaluating the effect of anti-VEGF on intractable macular edema. The OCT images at the 90-degree location could better show the inflammatory reaction of patients and also had better clinical significance for the prognosis evaluation of ME associated with inflammation.
Topics: Aged; Angiogenesis Inhibitors; Aqueous Humor; Female; Gene Expression Regulation; Humans; Interleukin-8; Macular Edema; Male; Middle Aged; Tomography, Optical Coherence; Treatment Outcome; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A
PubMed: 34211611
DOI: 10.1155/2021/5552824 -
Veterinary Ophthalmology May 2014To evaluate diagnostic utility of aqueous humor analysis in animals with anterior uveitis.
OBJECTIVE
To evaluate diagnostic utility of aqueous humor analysis in animals with anterior uveitis.
ANIMALS
Client-owned dogs (n = 12) and cats (n = 10).
PROCEDURES
Examination findings and diagnostic test results including aqueous humor cytology were compared.
RESULTS
Disease duration prior to aqueocentesis was not significantly different between dogs with idiopathic anterior uveitis and those with an etiologic diagnosis, but was shorter in cats with feline infectious peritonitis (FIP) than those with idiopathic uveitis. Microbial nucleic acids, antigens, or antibodies against them were seldom found in blood/serum; however, serum feline coronavirus titers ≥1:6400 were detected only in cats with FIP. Aqueous humor cytology was diagnostic in no cats and two dogs, both with neoplasia. Although aqueous humor contained predominantly neutrophils in cats with FIP and large reactive lymphocytes and plasma cells appeared more frequent in cats with idiopathic uveitis, neither clinical nor cytologic assessment of anterior chamber contents differed significantly between cats with idiopathic or FIP-associated uveitis. Cytologically assessed plasma cell number was correlated with keratic precipitates and disease duration. Clinically detectable hyphema and cytologic erythrocyte number were correlated. However, cytologic cell grades and clinical grade of flare or cell numbers within the anterior chamber were not correlated.
CONCLUSIONS
Aqueous humor cytology permitted diagnosis of neoplasia in dogs with anterior uveitis but was generally not helpful in cats. Poor correlation between clinical and cytologic assessment of cell numbers and type within the anterior chamber dictates that clinical grading should not be the sole criterion for electing to perform aqueocentesis.
Topics: Animals; Aqueous Humor; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Male; Uveitis, Anterior
PubMed: 23910096
DOI: 10.1111/vop.12075 -
PloS One 2016To investigate the aqueous humor proteome in patients with glaucoma and a control group.
PURPOSE
To investigate the aqueous humor proteome in patients with glaucoma and a control group.
METHOD
Aqueous humor was obtained from five human donors diagnosed with primary open angle glaucoma (POAG) and five age- and sex-matched controls undergoing cataract surgery. Quantitative proteome analysis of the aqueous humor by hyper reaction monitoring mass spectrometry (HRM-MS) based on SWATH technology was performed.
RESULTS
Expression levels of 87 proteins were found to be different between glaucomatous and control aqueous humor. Of the 87 proteins, 34 were significantly upregulated, whereas 53 proteins were downregulated in the aqueous humor from glaucoma patients compared to controls. Differentially expressed proteins were found to be involved in cholesterol-related, inflammatory, metabolic, antioxidant as well as proteolysis-related processes.
CONCLUSION
Glaucoma leads to profound changes to the aqueous humor proteome consistent with an altered metabolic state, an inflammatory response and impaired antioxidant defense.
Topics: Aged; Aged, 80 and over; Aqueous Humor; Case-Control Studies; Female; Glaucoma; Humans; Male; Middle Aged; Proteome; Up-Regulation
PubMed: 27788204
DOI: 10.1371/journal.pone.0165314 -
Survey of Ophthalmology 1987Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the... (Review)
Review
Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the formation of a filtering bleb. Aqueous in the subconjunctival space may then exit by multiple pathways. Bleb failure most often results from fibroblast proliferation and subconjunctival fibrosis. Factors associated with an increased risk of bleb failure include youth, aphakia, active anterior segment neovascularization, inflammation, previously failed glaucoma filtering surgery, and, possibly, race. Several surgical and pharmacologic techniques have recently been introduced to enhance success in eyes with poor surgical prognoses. To elucidate the scientific rationale of these methods, we summarize the process of wound healing after glaucoma filtering surgery and describe postoperative clinical and histopathologic features, factors which may affect success, and specific methods to improve surgical success.
Topics: Adrenal Cortex Hormones; Animals; Aqueous Humor; Disease Models, Animal; Glaucoma; Humans; Methods; Wound Healing
PubMed: 3328315
DOI: 10.1016/0039-6257(87)90091-9 -
Acta Ophthalmologica Sep 2020To evaluate the concentrations of pro-inflammatory cytokines in tear and aqueous humour of patients with primary open-angle glaucoma (POAG), relative to healthy controls.
PURPOSE
To evaluate the concentrations of pro-inflammatory cytokines in tear and aqueous humour of patients with primary open-angle glaucoma (POAG), relative to healthy controls.
METHOD
Tear and aqueous humour samples were collected from 29 healthy controls and 27 POAG patients. Twenty-seven inflammatory cytokines were analysed: interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, platelet-derived growth factor, regulated on activation normal T cell expressed and secreted, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF).
RESULTS
In tear samples of glaucoma patients, an increase in IL-4, IL-12, IL-15, FGF-basic and VEGF was observed, as well as a decrease in MIP-1a relative to the control group (p < 0.05). IL-5, IL-12, IL-15, IFN-γ and MIP-1a were significantly higher in aqueous humour of glaucoma eyes (p < 0.05). A poor correlation between cytokine levels in tear and aqueous humour was observed.
CONCLUSION
The different profiles of inflammatory marker expression of patients with POAG and healthy controls confirm the inflammatory activity of the pathology, indicating that some of them could be used as potential biomarkers of this disease.
Topics: Aqueous Humor; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Glaucoma, Open-Angle; Humans; Male; Tears
PubMed: 32043817
DOI: 10.1111/aos.14374