Effects of Sex Hormones on Ocular Blood Flow and Intraocular Pressure in Primary Open Angle Glaucoma: A Review

Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and visual field loss. Some speculate that gender plays a role in the risk of developing POAG and that the physiologic differences between men and women may be attributed to the variable effects of sex hormones on intraocular pressure (IOP), ocular blood flow, and/or neuroprotection. Estrogen, in the form of premenopausal status, pregnancy, and post-menopausal hormone therapy is associated with increase in ocular blood flow, decrease in IOP and neuroprotective properties. The vasodilation caused by estrogen and its effects on aqueous humor outflow may contribute. On the other hand, although testosterone may have known effects in the cardiovascular and cerebrovascular systems, there is no consensus as to its effects in ocular health or POAG. With better understanding of sex hormones in POAG, sex hormone-derived preventative and therapeutic considerations in disease management may provide for improved gender-specific patient care

Outflow Facility Effects of 3 Schlemm’s Canal Microinvasive Glaucoma Surgery Devices

Purpose To study the effect of 3 Schlemm’s canal (SC) microinvasive glaucoma surgery (MIGS) devices on outflow facility. Design Paired comparisons, randomized design, baseline-controlled study. Participants Thirty-six pairs of dissected anterior segments from donated human eye bank eyes without glaucoma were studied. A baseline measurement was collected from each eye to serve as its control. Methods Using a constant pressure perfusion method, outflow facility was measured in paired eyes from human donors. Measurements were made at perfusion pressures of 10 mmHg, 20 mmHg, 30 mmHg, and 40 mmHg. Outflow facility was measured before (baseline control) and after the implantation of an SC glaucoma drainage device or sham procedure. Three sets of experiments were carried out comparing 1 and 2 iStent Trabecular Micro-Bypass Stents and 2 iStent Inject implants with the Hydrus Microstent. Main Outcome Measures Change in outflow facility from baseline or contralateral eye. Results After Hydrus placement, the outflow facility increased from 0.23±0.03 μl/minute per millimeter of mercury at baseline to 0.38±0.03 μl/minute per millimeter of mercury (P < 0.001). The percent increase in outflow facility was 79±21% for the Hydrus and 11±16% for the 2 iStent Inject devices, a difference that was significant (P = 0.018). Outflow facility with 1 iStent (0.38±0.07 μl/minute per millimeter of mercury) was greater than baseline (0.28±0.03 μl/minute per millimeter of mercury; P = 0.031). The 1 iStent showed a greater increase in outflow facility from baseline (0.10±0.04 μl/minute per millimeter of mercury) compared with the sham procedure (–0.08±0.05 μl/minute per millimeter of mercury; P = 0.042). No other significant differences were found. Conclusions The longer the MIGS device, and thus the more SC that it dilates, the greater the outflow facility

Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications

<p>Abstract</p> <p>Background</p> <p>Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP.</p> <p>Methods</p> <p>Ten patients with type 1 diabetes and ten healthy age- and weight-matched controls were studied. Aqueous flow was measured by fluorophotometry during a hyperinsulinemic-euglycemic clamp (insulin 2 mU/kg/min). Intraocular pressure was measured by tonometry at -10, 90 and 240 minutes from the start of the clamp, and outflow facility was measured by tonography at 240 minutes.</p> <p>Results</p> <p>During conditions of identical glucose and insulin concentrations, mean aqueous flow was lower by 0.58 μl/min in the diabetes group compared to controls (2.58 ± 0.65 versus 3.16 ± 0.66 μl/min, respectively, mean ± SD, p = 0.07) but statistical significance was not reached. Before the clamp, IOP was higher in the diabetes group (22.6 ± 3.0 mm Hg) than in the control group (19.3 ± 1.8 mm Hg, p = 0.01) but at 90 minutes into the clamp, and for the remainder of the study, IOP was reduced in the diabetes group to the level of the control group. Ocular pulse amplitude and outflow facility were not different between groups. Systolic blood pressure was significantly higher in the diabetes group, but diastolic and mean arterial pressures were not different.</p> <p>Conclusions</p> <p>We conclude that compared to healthy participants, patients with type 1 diabetes having microalbuminuria and retinopathy have higher IOPs that are normalized by hyperinsulinemia. During the clamp, a reduction in aqueous flow was not statistically significant.</p

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

Quantitative Proteomic Analysis of Human Aqueous Humor Using iTRAQ 4plex Labeling

iTRAQ 4plex method enables multiplexing of up to four samples for simultaneous quantitation to improve sensitivity and scope of proteomic analysis. Here, we describe iTRAQ 4plex labeling of human aqueous humor specimens followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and data analysis for peptide identification and quantitation using Proteome Discoverer software. The protocol can be applied for other animals as well; however, pooling of specimens may be required to obtain sufficient amount of protein for labeling

Endothelial Glycocalyx Morphology in Different Flow Regions of the Aqueous Outflow Pathway of Normal and Laser-Induced Glaucoma Monkey Eyes

Glycocalyx morphology was examined in the trabecular outflow pathway of monkey eyes with and without experimental glaucoma. Laser burns were administered along ~270 degrees of the trabecular meshwork (TM) of one eye (n = 6) or both eyes (n = 2) of each monkey until intraocular pressure remained elevated. Portions of the TM were not laser-treated. Unlasered eyes (n = 6) served as controls. Enucleated eyes were perfused at 15 mmHg to measure the outflow facility, perfused with fluorescein to evaluate the outflow pattern, perfusion-fixed for glycocalyx labeling, and processed for electron microscopy. Coverage and thickness of the glycocalyx were measured in the TM, Schlemm’s canal (SC), collector channels (CCs), intrascleral veins (ISVs), and episcleral veins (ESVs) in non-lasered regions and high- and low-flow regions of controls. Compared to controls, laser-treated eyes had decreased outflow facility (p = 0.02). Glycocalyx thickness increased from the TM to ESVs in non-lasered regions and controls (p p < 0.05). In lasered regions, TM, SC, and CCs were partly to completely obliterated, and ISVs and ESVs displayed minimal glycocalyx. Whether the glycocalyx is decreased in the trabecular outflow pathway of human glaucomatous eyes warrants investigation

Shotgun Sphingolipid Analysis of Human Aqueous Humor

This protocol provides a step-by-step guide to shotgun sphingolipid analysis of aqueous humor. We describe the Bligh and Dyer crude lipid extraction method and electrospray ionization tandem mass spectrometry (ESI-MS/MS) coupled with MZmine 2.21 data processing for identification and ratiometric quantitation of sphingosine, sphingosine-1-phosphate, sphingomyelin, and ceramide

Effects of rho kinase inhibitors on intraocular pressure and aqueous humor dynamics in nonhuman primates and rabbits

Purpose: This study examines the effects of 2 Rho kinase inhibitors on intraocular pressure (IOP) and aqueous humor dynamics. Methods: IOPs of New Zealand albino rabbits with ocular normotension and cynomolgus macaques (nonhuman primate, NHP) with chronic unilateral laser-induced glaucoma were measured at baseline and periodically after a 9 a.m. dose of H-1152, Y-27632, or vehicle. In a separate group of NHPs, aqueous flow, outflow facility, uveoscleral outflow, and IOP were determined after treatment with Y-27632 or vehicle control. Results: Decreases in IOP were found in rabbits (n = 5) at 6 h after one dose of 2% Y-27632 (29%, P = 0.0002) or 1% H-1152 (35%, P = 0.0001), and in hypertensive eyes of NHPs (n = 7-9) at 3 h after one dose of 2% Y-27632 (35%, P = 0.005) or 1% H-1152 (51%, P = 0.0003). With 2 doses of 1% Y-27632 or vehicle in NHP hypertensive eyes (n = 12), significant drug effects were IOP reduction of 28% (P = 0.05) at 2.5 h after the second dose and increases in aqueous flow (36%; P = 0.013), uveoscleral outflow (59%, P = 0.008), and outflow facility (40%; P = 0.01). In normotensive eyes of the same animals, aqueous flow increased by 21% (P = 0.03). No significant change was found in any of the other parameters. Conclusions: Y-27632 and H-1152 lower IOP in rabbits and hypertensive eyes of NHPs for at least 6 h after single doses. The Y-27632 effect on IOP in hypertensive NHP eyes is caused by increases in outflow facility and uveoscleral outflow. An increase in aqueous humor formation attenuates but does not prevent an IOP decrease