Fluid shear modulates many biological properties. How shear mechanosensing occurs in the extracellular matrix (ECM) and is transduced into cytoskeletal change remains unknown. Cochlin is an ECM protein of unknown function. Our investigation using a comprehensive spectrum of cutting-edge techniques has resulted in following major findings: (1) over-expression and down-regulation of cochlin increase and decrease intraocular pressure (IOP), respectively. The overexpression was achieved in DBA/2J-Gpnmb(+)/SjJ using lentiviral vectors, down-regulation was achieved in glaucomatous DBA/2J mice using targeted disruption (cochlin-null mice) and also using lentiviral vector mediated shRNA against cochlin coding region; (2) reintroduction of cochlin in cochlin-null mice increases IOP; (3) injection of exogenous cochlin also increased IOP; (4) increasing perfusion rates increased cochlin multimerization, which reduced the rate of cochlin proteolysis by trypsin and proteinase K; The cochlin multimerization in response to shear stress suggests its potential mechanosensing. Taken together with previous studies, we show cochlin is involved in regulation of intraocular pressure in DBA/2J potentially through mechanosensing of the shear stress.

Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5-10 per group) were subjected to IOP challenge (10-120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.

Laser in situ keratomileusis (LASIK), a refractive surgery procedure is being performed in a large number among people with refractive errors. In all the people undergoing the procedure, there is a potential risk to misdiagnose the glaucoma disease due to changes in central corneal thickness (CCT). In subjects who have undergone laser refractive interventions, intraocular tension may be lower and underestimated, and this can lead to later detection of glaucoma.

To test for causality with regard to the association between blood pressure (BP) and intraocular pressure (IOP) and glaucoma.

Many experiments have documented the response of intraocular pressure (IOP) to postural change. External forces caused by gravitational orientation change produce a dynamic response that is encountered every day during normal activities. Tilting the body at a small downward angle is also relevant to studying the effects of hypogravity (spaceflight), including ocular changes. We examined data from 36 independent datasets from 30 articles on IOP response to postural change, representing a total population of 821 subjects (≥1173 eyes) with widely varying initial and final postures. We confirmed that IOP was well predicted by a simple quantity, namely the hydrostatic pressure at the level of the eye, although the dependence was complex (nonlinear). Our results show that posturally induced IOP change can be explained by hydrostatic forcing plus an autoregulatory contribution that is dependent on hydrostatic effects. This study represents data from thousands of IOP measurements and provides insight for future studies that consider postural change in relation to ocular physiology, intraocular pressure, ocular blood flow and aqueous humor dynamics.

Pneumoperitoneum during laparoscopy can produce changes in intraocular pressure (IOP) that may be influenced by several factors. In this study, we investigated changes in IOP during laparoscopy with different positioning.

Interscalene block (ISB) is commonly associated with Horner's syndrome due to spread of local anesthetic to the cervical sympathetic chain. Postganglionic neurons that originate from superior cervical ganglia form the sympathetic innervation of eye. Decrease in sympathetic tone may change intraocular pressure (IOP) and ocular perfusion pressure (OPP). The aim of the study was to investigate whether ISB affects IOP and/or OPP.

The rapidly increasing utilization of smartphones makes ophthalmic problems associated with their use an important issue. This prospective study aimed to determine whether using a smartphone to view visual material is associated with a change in the intraocular pressure (IOP), and to determine which groups of factors best predict the time-dependent increase in IOP with smartphone use. This study included 158 eyes (127 glaucomatous and 31 healthy eyes) recruited from Seoul National University Bundang Hospital. Participants performed a sustained fixation task consisting of watching a movie on a smartphone screen for 30 minutes continuously at a viewing distance of 30 cm. A small but statistically significant time-dependent increase in IOP was observed while viewing a movie on a smartphone, being 10.6 ± 3.1, 11.0 ± 3.3, 11.2 ± 3.4, and 11.6 ± 3.5 mmHg before and 5, 10, and 30 minutes after the fixation task, respectively (P < 0.0001). Recursive partitioning tree analysis revealed that a shallower anterior chamber (<2.32 mm) was the strongest predictive factor for faster time-dependent increase in IOP (0.68 mmHg/minute). A higher visual field mean deviation (≥-0.22 dB), and an older age (≥48 years) were the second and third most influential factors associated with the rate of IOP increase (0.59 and 0.15 mmHg/minute, respectively).

Glaucoma-like neuropathies can be experimentally induced by disturbing aqueous outflow from the eye, resulting in intraocular pressure (IOP) changes that are variable in magnitude and time course and permanent in duration. This study introduces a novel method of glaucoma induction that offers researchers round-the-clock measurement and reversible control of IOP for the first time. One eye of Brown-Norway rats was implanted with a cannula tethered to a pressure sensor and aqueous reservoir. IOP was raised 10 mmHg for weeks-to-months in treated animals and unaltered in control animals. Counts of Brn3a-expressing retinal ganglion cells (RGCs) in implanted eyes were indistinguishable from non-implanted eyes in control animals and 15 ± 2%, 23 ± 4%, and 38 ± 4% lower in animals exposed to 2, 4, and 9 weeks of IOP elevation. RGC loss was greater in peripheral retina at 2 weeks and widespread at longer durations. Optic nerves also showed progressive degeneration with exposure duration, yet conventional outflow facility of implanted eyes was normal (24.1 ± 2.9 nl/min/mmHg) even after 9-weeks elevation. Hence, this infusion-based glaucoma model exhibits graded neural damage with unimpaired outflow pathways. The model further revealed a potentially-significant finding that outflow properties of rat eyes do not remodel in response to chronic ocular hypertension.

We investigate 24-hour intraocular pressure (IOP) fluctuation patterns and the influence of body position on IOP in a chronic ocular hypertension (COHT) monkey model.

It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a major cause of blindness. THC likely acts via one of the known cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this has never been determined explicitly. Cannabidiol (CBD) is a second major constituent of cannabis that has been found to be without effect on IOP in most studies.

The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases.

Intraocular Pressure (IOP) is an important and modifiable risk factor for glaucoma progression. IOP fluctuations and spikes often remain undetected despite clinical routine examinations. Therefore telemetric IOP measurement systems with continuous IOP monitoring can provide major advantages in glaucoma surveillance. To the best of our knowledge, this is the first study to investigate implantable telemetric suprachoroidal IOP sensors. Six novel telemetric pressure transducers were implanted in the suprachoroidal space of 6 eyes from 6 New Zealand White rabbits. Functionality of each microsensor was verified 1, 4, 8, 12 and 30 weeks after implantation. After cannulation of the anterior chamber different intracameral pressure levels were generated using a height adjustable water column. Telemetric assessed IOP and intracameral pressure were analysed using scatter plots and Bland-Altman analysis (95% CI). Mean bias (limits of agreement) 1, 4, 8, 12 and 30 weeks after implantation was 0.14 mmHg (-2.04 to 2.31 mmHg), 0.01 mmHg (-2.83 to 2.86 mmHg), 0.62 mmHg (-2.08 to 3.32 mmHg), 0.47 mmHg (-3.04 to 3.98 mmHg) and 0.33 mmHg (-2.75 to 3.42 mmHg) respectively. Ophthalmological examinations showed no signs of conjunctival, scleral, choroidal or retinal lesions. Histological analyses revealed a small band of fibrosis next to the implantation site but showed no signs of inflammation, necrosis or other pathologies. Implantable telemetric suprachoroidal pressure sensors provided promising concordance between telemetric and intracameral IOP values. Clinical and histological examinations revealed good biocompatibility 30 weeks after implantation. A major advantage of the suprachoroidal approach is that the anterior chamber stays unaffected during implantation. Therefore the procedure can be performed regardless of the lens status and any anterior chamber pathologies.

CD44 plays major roles in multiple physiologic processes. The ectodomain concentration of the CD44 receptor, soluble CD44 (sCD44), is significantly increased in the aqueous humor of primary open-angle glaucoma (POAG). The purpose of this study was to determine if adenoviral constructs of CD44 and isolated 32-kDa sCD44 change intraocular pressure (IOP) in vivo and aqueous outflow resistance in vitro.

To assess changes in the position of lamina cribrosa pores (LCPs) induced by acute intraocular pressure (IOP) elevation.

The neuroregulatory center of intraocular pressure (IOP) is located in the hypothalamus. An efferent neural pathway exists between the hypothalamic nuclei and the autonomic nerve endings in the anterior chamber of the eye. This study was designed to investigate whether the paraventricular hypothalamic nucleus (PVH) regulates IOP as the other nuclei do.

To investigate the effect of reading or writing on a smartphone in terms of intraocular pressure (IOP) changes.

To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR).

Functional adaptation to ambient light is a key characteristic of retinal ganglion cells (RGCs), but little is known about how adaptation is affected by factors that are harmful to RGC health. We explored adaptation-induced changes to RGC physiology when exposed to increased intraocular pressure (IOP), a major risk factor for glaucoma.

Glaucoma is a group of eye conditions that damage the optic nerve, the health of which is vital for vision. The key risk factor for the development and progression of this disease is increased intraocular pressure (IOP). Implantable glaucoma drainage devices have been developed to divert aqueous humor from the glaucomatous eye as a means of reducing IOP. The artificial drainage pathway created by these devices drives the fluid into a filtering bleb. The long-term success of filtration surgery is dictated by the proper functioning of the bleb and overlying Tenon's and conjunctival tissue. To better understand the influence of the health condition of these tissues on IOP, we have developed a mathematical model of fluid production in the eye, its removal from the anterior chamber by a particular glaucoma implant-the PRESERFLO® MicroShunt-, drainage into the bleb and absorption by the subconjunctival vasculature. The mathematical model was numerically solved by commercial FEM package COMSOL. Our numerical results of IOP for different postoperative conditions are consistent with the available evidence on IOP outcomes after the implantation of this device. To obtain insight into the adjustments in the implant's hydrodynamic resistance that are required for IOP control when hypotony or bleb scarring due to tissue fibrosis take place, we have simulated the flow through a microshunt with an adjustable lumen diameter. Our findings show that increasing the hydrodynamic resistance of the microshunt by reducing the lumen diameter, can effectively help to prevent hypotony. However, decreasing the hydrodynamic resistance of the implant will not sufficiently decrease the IOP to acceptable levels when the bleb is encapsulated due to tissue fibrosis. Therefore, to effectively reduce IOP, the adjustable glaucoma implant should be combined with a means of reducing fibrosis. The results reported herein may provide guidelines to support the design of future glaucoma implants with adjustable hydrodynamic resistances.