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Investigative Ophthalmology & Visual... Aug 2020Conventional wisdom posits that aqueous humor leaves the eye by passive bulk flow without involving energy-dependent processes. However, recent studies have shown that...
PURPOSE
Conventional wisdom posits that aqueous humor leaves the eye by passive bulk flow without involving energy-dependent processes. However, recent studies have shown that active processes, such as cell contractility, contribute to outflow regulation. Here, we examine whether inhibiting cellular metabolism affects outflow facility in mice.
METHODS
We measured outflow facility in paired enucleated eyes from C57BL/6J mice using iPerfusion. We had three Experimental Sets: ES1, perfused at 35°C versus 22°C; ES2, perfused with metabolic inhibitors versus vehicle at 35°C; and ES3, perfused at 35°C versus 22°C in the presence of metabolic inhibitors. Inhibitors targeted glycolysis and oxidative phosphorylation (2-deoxy-D-glucose, 3PO and sodium azide). We also measured adenosine triphosphate (ATP) levels in separate murine anterior segments treated like ES1 and ES2.
RESULTS
Reducing temperature decreased facility by 63% [38%, 78%] (mean [95% confidence interval (CI)], n = 10 pairs; P = 0.002) in ES1 after correcting for changes in viscosity. Metabolic inhibitors reduced facility by 21% [9%, 31%] (n = 9, P = 0.006) in ES2. In the presence of inhibitors, temperature reduction decreased facility by 44% [29%, 56%] (n = 8, P < 0.001) in ES3. Metabolic inhibitors reduced anterior segment adenosine triphosphate (ATP) levels by 90% [83%, 97%] (n = 5, P<<0.001), but reducing temperature did not affect ATP.
CONCLUSIONS
Inhibiting cellular metabolism decreases outflow facility within minutes. This implies that outflow is not entirely passive, but depends partly on energy-dependent cellular processes, at least in mice. This study also suggests that there is a yet unidentified mechanism, which is strongly temperature-dependent but metabolism-independent, that is necessary for nearly half of normal outflow function in mice.
Topics: Animals; Aqueous Humor; Deoxyglucose; Glycolysis; Male; Mice; Mice, Inbred C57BL; Oxidative Phosphorylation; Perfusion; Pyridines; Sodium Azide
PubMed: 32845955
DOI: 10.1167/iovs.61.10.45 -
European Journal of Pharmacology Sep 2016Primary open angle glaucoma (POAG) is an optic neuropathy and an irreversible blinding disease. The etiology of glaucoma is not known but numerous risk factors are... (Review)
Review
Primary open angle glaucoma (POAG) is an optic neuropathy and an irreversible blinding disease. The etiology of glaucoma is not known but numerous risk factors are associated with this disease including aging, elevated intraocular pressure (IOP), race, myopia, family history and use of steroids. In POAG, the resistance to the aqueous humor drainage is increased leading to elevated IOP. Lowering the resistance and ultimately the IOP has been the only way to slow disease progression and prevent vision loss. The primary drainage pathway comprising of the trabecular meshwork (TM) is made up of relatively large porous beams surrounded by extracellular matrix (ECM). Its juxtacanalicular tissue (JCT) or the cribriform meshwork is made up of cells embedded in dense ECM. The JCT is considered to offer the major resistance to the aqueous humor outflow. This layer is adjacent to the endothelial cells forming Schlemm's canal, which provides approximately 10% of the outflow resistance. The ECM in the TM and the JCT undergoes continual remodeling to maintain normal resistance to aqueous humor outflow. It is believed that the TM is a major contributor of ECM proteins and evidence points towards increased ECM deposition in the outflow pathway in POAG. It is not clear how and from where the ECM components emerge to hinder the normal aqueous humor drainage. This review focuses on the involvement of the ECM in ocular hypertension and glaucoma and the mechanisms by which various ocular hypotensive drugs, both current and emerging, target ECM production, remodeling, and deposition.
Topics: Animals; Aqueous Humor; Extracellular Matrix; Eye Diseases; Humans
PubMed: 27112663
DOI: 10.1016/j.ejphar.2016.04.048 -
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 -
American Journal of Ophthalmology Mar 1956
Topics: Aqueous Humor
PubMed: 13302342
DOI: 10.1016/0002-9394(56)91253-3 -
A.M.A. Archives of Ophthalmology Dec 1955
Topics: Aqueous Humor
PubMed: 13268134
DOI: 10.1001/archopht.1955.00930020805001 -
Investigative Ophthalmology & Visual... Nov 1979The composition of rhesus monkey aqueous humor has been studied in large-volume, pooled samples. Replicate determinations of the concentrations of a number of...
The composition of rhesus monkey aqueous humor has been studied in large-volume, pooled samples. Replicate determinations of the concentrations of a number of constituents have been carried out for both aqueous humor and serum from large veins by means of automatic analyzing equipment. Since aqueous humor has been obtained by anterior chamber paracentesis, it is a mixture of anterior and posterior chamber aqueous. When compared to serum, the pooled aqueous contains an excess of chloride, bicarbonate, ascorbate, lactate, uric acid, and several neutral amino acids. Rhesus monkey aqueous humor is deficient in calcium, urea nitrogen, phosphates, glucose, protein, creatinine, iron, bilirubin, cholesterol, triglycerides, a number of serum enzymes, acidic and basic amino acids, and several neutral amino acids. Sodium, potassium, magnesium, and two neutral amino acids (cysteine and valine) are of equal concentration in aqueous humor and serum. Glutathione concentration is very low in both aqueous humor and serum. Pooled rhesus monkey aqueous humor and serum are isosmolar, with measured osmolality being about 303 mOsm. Based upon the chemical analysis, a new solution has been formulated to substitute for primate aqueous humor during anterior ocular perfusion. This new solution causes very little change in the physiologic integrity of the outflow pathways during prolonged, repeated perfusion. In this respect, its effects are very similar to those of pooled rhesus monkey aqueous humor during perfusion of rhesus monkey eyes. In contrast, perfusion of rhesus monkey eyes with glutathione-bicarbonate-Ringer's solution has been shown to cause progressive increase of the total facility. To minimize physiologic alterations during operative procedures, a solution similar to this new one could be formulated for irrigation of the inside of the human eye.
Topics: Animals; Anterior Chamber; Aqueous Humor; Haplorhini; Macaca mulatta; Ophthalmic Solutions; Osmolar Concentration; Perfusion
PubMed: 116968
DOI: No ID Found -
Transactions of the Ophthalmological... 1986In hypotony, where the intraocular pressure is lower than the episcleral venous pressure, aqueous humour outflow must be via unconventional channels, such as uveoscleral... (Review)
Review
In hypotony, where the intraocular pressure is lower than the episcleral venous pressure, aqueous humour outflow must be via unconventional channels, such as uveoscleral outflow pathways. The level of intraocular pressure will be determined by the rate of aqueous humour production and the facility of unconventional outflow. The facility of unconventional outflow has been shown to be increased in eyes with experimentally-induced hypotony from cyclodialysis, ciliochoroidal detachment, iridocyclitis, or retinal detachment. Aqueous humour production is reduced in eyes with hypotony during the acute phase following cyclodialysis, and in eyes with iridocyclitis or rhegmatogenous retinal detachment. Chronic cyclodialysis or ciliochoroidal detachment does not lead to reduced aqueous humour production, if unassociated with iridocyclitis. Detachment of the ciliary body in hypotony is often associated with, but does not appear to cause, reduced aqueous humour formation. Apart from treatment of the specific cause of hypotony, reduction of the accompanying inflammatory response is essential for normalisation of aqueous dynamics and intraocular pressure.
Topics: Animals; Aqueous Humor; Choroid; Ciliary Body; Haplorhini; Humans; Intraocular Pressure; Retinal Detachment; Uveal Diseases; Uveitis, Anterior
PubMed: 3099433
DOI: No ID Found -
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 -
International Ophthalmology Dec 2017The opacification of Akreos Adapt (Bausch & Lomb, Rochester; NY) intraocular lens (IOL) has been previously reported in Literature. A metabolic change in aqueous humour...
BACKGROUND AND PURPOSE
The opacification of Akreos Adapt (Bausch & Lomb, Rochester; NY) intraocular lens (IOL) has been previously reported in Literature. A metabolic change in aqueous humour was considered as the main trigger factor to IOL opacification. We report our case and discuss the association with Ex-PRESS, highlighting the particular pattern of IOL opacification and its possible relation with the intraocular convective motions of the aqueous.
MATERIAL AND METHODS
We analyzed our case using both digital slit lamp acquisition and OCT Visante (Zeiss, Germany) images. A literature review was conducted to evaluate our results with that previously reported.
CONCLUSION
The role of a relative stationary flow was reported as suggested concurrent mechanism in IOL opacification phenomenon.
Topics: Adult; Aqueous Humor; Calcium Compounds; Cataract; Female; Humans; Lens Implantation, Intraocular; Lenses, Intraocular
PubMed: 27942981
DOI: 10.1007/s10792-016-0400-7 -
Advances in Ophthalmology =... 1980
Topics: Adolescent; Adult; Aged; Animals; Anterior Chamber; Aqueous Humor; Blood Proteins; Cattle; Child; Child, Preschool; Ciliary Body; Electrophoresis; Eye Diseases; Eye Proteins; Female; Humans; Male; Microscopy, Electron, Scanning; Middle Aged
PubMed: 7361630
DOI: No ID Found