In Vivo Quantification of Anterior and Posterior Chamber Volumes in Mice: Implications for Aqueous Humor Dynamics

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 18 - 18

Published: Jan. 8, 2025

Purpose: Aqueous humor inflow rate, a key parameter influencing aqueous dynamics, is typically measured by fluorophotometry. Analyzing fluorophotometric data depends, inter alia, on the volume of in anterior chamber but not posterior chamber. Previous studies rate mice have assumed ratio anterior:posterior volumes to be similar those humans. Our goal was measure and facilitate better estimates rates. Methods: We used standard near-infrared (NIR) optical coherence tomography (OCT) robotic visible-light OCT (vis-OCT) visualize, reconstruct, quantify chambers mouse eye vivo. histology micro-computed (CT) scans validate relevant landmarks from ex vivo tissues measurement. Results: Posterior 1.1 times BALB/cAnNCrl mice, that is, constitutes about 47% total volume, which very dissimilar situation Anterior 2-month-old C57BL6/J were 1.55 ± 0.36 µL (n = 10) 2.05 0.25 10), respectively. This implies previous likely overestimated approximately twofold. Conclusions: It necessary reassess previously reported rates and, thus, dynamics mouse. For example, we now estimate only 0% 15% drains via pressure-independent (unconventional) route, seen humans monkeys.

Language: Английский

---

Glaucoma Animal Models beyond Chronic IOP Increase

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 906 - 906

Published: Jan. 11, 2024

Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play pivotal role in glaucoma onset progression. For example, it known that excitotoxicity, immunological alterations, ischemia, oxidative stress contribute to neurodegeneration disease. To study these effects discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various beyond IOP. We introduce genetically modified mice, e.g., optineurin E50K knock-in or glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting analogue N-methyl-D-aspartate intravitreally, which leads rapid RGC degeneration. explore contribution immune system, experimental autoimmune model serve useful tool. Here, immunization with antigens led glaucoma-like damage. The ischemic mechanism inducing high IOP for certain amount time rodents, followed reperfusion. Thereby, damage retina optic nerve occurs rapidly after ischemia/reperfusion. Lastly, discuss importance crush systems normal-tension glaucoma. summary, increase utilized.

Language: Английский

---

Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease

Progress in Retinal and Eye Research, Journal Year: 2022, Volume and Issue: 91, P. 101094 - 101094

Published: June 18, 2022

Language: Английский

---

Morphological and biomechanical analyses of the human healthy and glaucomatous aqueous outflow pathway: Imaging-to-modeling

Computer Methods and Programs in Biomedicine, Journal Year: 2023, Volume and Issue: 236, P. 107485 - 107485

Published: March 15, 2023

Intraocular pressure (IOP) is maintained via a dynamic balance between the production of aqueous humor and its drainage through trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), Schlemm's canal (SC) endothelium conventional outflow pathway. Primary open angle glaucoma (POAG) often associated with IOP elevation that occurs due to an abnormally high resistance across Outflow tissues are viscoelastic actively interact dynamics two-way fluid-structure interaction coupling. While affects morphology stiffness tissues, their biomechanics hydrodynamics in eyes remain largely unknown. This research aims develop image-to-model method allowing pathway be studied. We used combination X-ray computed tomography scanning electron microscopy reconstruct high-fidelity, eye-specific, 3D microstructural finite element models healthy cellularized decellularized conditions. The TM/JCT/SC complex embedded beam elements were subjected physiological load boundary; stresses/strains flow state calculated using computational fluid dynamics. Based on resultant parameters pathway, primary site was JCT immediate vicinity SC inner wall, while majority occurred TM. TM showed 1.32-fold 1.13-fold larger thickness smaller space size (2.24-fold 1.50-fold) compared eyes. Characterizing accurate may significantly contribute constructing more accurate, robust, reliable models, can eventually help better understand regulation, humor, human model demonstrates proof concept for determining changes glaucomatous thus utilized cohorts donor where disease specificity, race, age, gender eye donors accounted for.

Language: Английский

---

Animal Models in Eye Research: Focus on Corneal Pathologies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16661 - 16661

Published: Nov. 23, 2023

The eye is a complex sensory organ that enables visual perception of the world. dysfunction any these tissues can impair vision. Conduction studies on laboratory animals are essential to ensure safety therapeutic products directly applied or injected into treat ocular diseases before eventually proceeding clinical trials. Among tissues, cornea has unique homeostatic and regenerative mechanisms for maintaining transparency refraction external light, which However, being outermost tissue exposed environment, particularly susceptible injury diseases. This review highlights evidence selecting appropriate better understand corneal diseases, rank as fifth leading cause blindness worldwide. development reliable human-relevant animal models is, therefore, valuable research tool understanding translating fundamental mechanistic findings, well assessing potential in humans. First, this emphasizes characteristics used research. Subsequently, it discusses current associated with human pathologies, their utility disease mechanisms, role translational patients.

Language: Английский

---

TRPV4 subserves physiological and pathological elevations in intraocular pressure

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Ocular hypertension (OHT) caused by mechanical stress and chronic glucocorticoid exposure reduces the hydraulic permeability of conventional outflow pathway. It increases risk for irreversible vision loss, yet healthy individuals experience nightly intraocular pressure (IOP) elevations without adverse lifetime effects. is not known which sensors regulate physiological vs. pathological OHT nor how they impact principal drainage pathway through trabecular meshwork (TM). We report that induced circadian rhythm, occlusion iridocorneal angle glucocorticoids requires activation TRPV4, a stretch-activated cation channel. Wild-type mice responded to nocturnal topical administration agonist GSK1016790A with IOP lowering, while intracameral injection elevated diurnal IOP. Microinjection TRPV4 antagonists HC067047 GSK2193874 lowered during phase in hypertensive eyes treated steroids or polystyrene microbeads. Conventional outflow-specific Trpv4 knockdown partial lowering occluded protected retinal neurons from injury. Indicating central role TRPV4-dependent mechanosensing outflow, doubled facility TM-populated steroid-treated 3D nanoscaffolds. Tonic signaling thus represents fundamental property TM biology as driver increased in vitroand vivo resistance. The TRPV4-dependence under conditions mimic primary secondary glaucomas could be explored novel target glaucoma treatments.

Language: Английский

---

Myocilin Gene Mutation Induced Autophagy Activation Causes Dysfunction of Trabecular Meshwork Cells

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: May 9, 2022

Trabecular meshwork dysfunction is the main cause of primary open angle glaucoma (POAG) associated with elevated intraocular pressure (IOP). Mutant myocilin causes mainly via elevating IOP. Previously we have found that accumulated Asn 450 Tyr (N450Y) mutant impairs human trabecular (TM) cells by inducing chronic endoplasmic reticulum (ER) stress response in vitro. However, it unclear how ER leads to TM damage and whether N450Y mutation POAG vivo. Here induces autophagy, which worsens cell viability, whereas inhibition autophagy increases viability decreases death cells. Furthermore, construct a transgenic mouse model (Tg-MYOCN450Y) Tg-MYOCN450Y mice exhibiting phenotypes: IOP elevation, retinal ganglion loss visual impairment. Consistent our published vitro studies, fails secrete into aqueous humor, actives mice, humor dynamics are altered mice. In summary, studies demonstrate activation correlated pathogenesis POAG.

Language: Английский

---

Intraocular pressure across the lifespan of Tg-MYOCY437H mice

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 241, P. 109855 - 109855

Published: March 5, 2024

Language: Английский

---

Viscoelastic Biomechanical Properties of the Conventional Aqueous Outflow Pathway Tissues in Healthy and Glaucoma Human Eyes

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(20), P. 6049 - 6049

Published: Oct. 13, 2022

Although the tissues comprising ocular conventional outflow pathway have shown strong viscoelastic mechanical response to aqueous humor pressure dynamics, properties of trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) inner wall are largely unknown. A quadrant anterior segment from two human donor eyes at low- high-flow (LF HF) regions was pressurized imaged using optical coherence tomography (OCT). finite element (FE) model TM, adjacent JCT, SC constructed beam elements were distributed in extracellular matrix (ECM) TM JCT represent anisotropic collagen. An inverse FE-optimization algorithm used calculate ECM/beam such that TM/JCT/SC OCT imaging data best matched over time. The ECM glaucoma showed significantly larger time-dependent shear moduli compared heathy tissues. Significantly also observed LF both healthy HF regions. stiffer less able respond dynamic IOP.

Language: Английский

---

The Effect of Intraocular Pressure Load Boundary on the Biomechanics of the Human Conventional Aqueous Outflow Pathway

Bioengineering, Journal Year: 2022, Volume and Issue: 9(11), P. 672 - 672

Published: Nov. 10, 2022

Aqueous humor outflow resistance in the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of conventional pathway actively contribute to intraocular pressure (IOP) regulation. Outflow is affected by dynamic gradient across TM, JCT, SC inner wall tissues. The effect implies presence a fluid-structure interaction (FSI) coupling between tissues aqueous humor. However, biomechanical interactions viscoelastic dynamics are largely unknown. A 3D microstructural finite element (FE) model healthy human eye TM/JCT/SC complex was constructed with elastic material properties for bulk extracellular matrix embedded cable elements. FE models were subjected both idealized physiologic IOP load boundary using FSI method. at equal IOPs showed similar stresses strains as well sensitive rate, resulting different mechanical hydrodynamic responses Transient fluctuations may cause relatively large difference ~20 mmHg very short time frame ~0.1 s, rate stiffening Rate reduces causes rate-dependent Thus, results suggest it necessary use that includes important role rate.

Language: Английский

---