Elevated Intraocular Pressure induces Ultrastructural Changes in the Trabecular Meshwork

Vecino, Elena; GaldósM,; Bayón, Alejandro; Fd, Rodríguez; Mico, Cristina López; Sc, Sharma

doi:10.4172/2157-7099.s3-007

Cited by 8 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,4,8,10,11 Unfortunately its general lack of polycromasia makes it unsuitable for photomicrography. Much better results are obtained for general work as well as for photomicrography (especially with the use of filters for the black and white film) with the methylene blue, azure II combinations.…”

Section: Discussionmentioning

confidence: 99%

Light Microscopic Studies on the Morphology of Tissues Embedded in Epoxy Resin

Kukurtchyan¹,

Karapetyan²,

Hayrapetyan³

2017

ECB

View full text Add to dashboard Cite

The best preservation of tissue structures for a long time has been reached by the embedding of tissues into epoxy resins. The aim of the current research is to show the potential of light microscopic studies on the research of blood vessels of tissues embedded and conservated in epoxide resins. Our results demonstrated that preservation of tissue in epoxide resins proved to be a convenient method for theirs studying under light microscope independently of the age and temperature conditions of the sample storage.

show abstract

Section: Discussionmentioning

confidence: 99%

Light Microscopic Studies on the Morphology of Tissues Embedded in Epoxy Resin

Kukurtchyan¹,

Karapetyan²,

Hayrapetyan³

2017

ECB

View full text Add to dashboard Cite

show abstract

“…Under dynamic fluidic transport conditions in vivo, rigid materials provide mechanical support to prevent degradation and structural collapses over time and viscous surfaces provide strong interactions with tissues to retain beads against shear forces and turbulence in AH flow 25, 26 . Current PS and latex microsphere models, which only consist of rigid materials without viscous surfaces, exhibit limited retention time and consequently require multiple injections to maintain IOP elevation over time 15, 27, 28 .…”

Section: Main Textmentioning

confidence: 99%

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

Hong,

Tian,

Glynn

et al. 2024

Preprint

View full text Add to dashboard Cite

Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable viscobeads technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4+-1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.

show abstract

“…3−5 Changes in physical properties of the HTM, such as the increase in stiffness (from 4 kPa in a healthy tissue to 80 kPa in a glaucomatous one), 6 alterations in extracellular matrix (ECM) protein expression, 7 or loss in its reparative capacity, can lead to increased outflow resistance, elevated IOP, and eventually glaucoma. 7,8 Although pathogenetic mechanisms that lead to IOP elevation are still unclear, previous studies have identified the juxtacanalicular tissue (JCT) region, the inner part of the HTM after uveoscleral and corneoscleral layers, in conjunction to the inner wall region of Schlemm's canal as the primary site of outflow resistance due to the reduced pore size (0.5−2 μm) present in the JCT 9,10 (Figure 1A).…”

Section: ■ Introductionmentioning

confidence: 99%

“…Primary open-angle glaucoma is the most predominant form of glaucoma, a complex neurodegenerative disease often associated with elevated intraocular pressure (IOP) . Most of the currently available glaucoma therapies target aqueous humor (AH) production or the uveoscleral outflow pathway, which does not address the human trabecular meshwork (HTM) pathway (the conventional outflow pathway) responsible for 70–90% of AH drainage into the systemic circulation. − Changes in physical properties of the HTM, such as the increase in stiffness (from 4 kPa in a healthy tissue to 80 kPa in a glaucomatous one), alterations in extracellular matrix (ECM) protein expression, or loss in its reparative capacity, can lead to increased outflow resistance, elevated IOP, and eventually glaucoma. , Although pathogenetic mechanisms that lead to IOP elevation are still unclear, previous studies have identified the juxtacanalicular tissue (JCT) region, the inner part of the HTM after uveoscleral and corneoscleral layers, in conjunction to the inner wall region of Schlemm's canal as the primary site of outflow resistance due to the reduced pore size (0.5–2 μm) present in the JCT , (Figure A).…”

Section: Introductionmentioning

confidence: 99%

Nanofibrous PCL-Based Human Trabecular Meshwork for Aqueous Humor Outflow Studies

Bikuna-Izagirre,

Aldazabal,

Extramiana

et al. 2023

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

Primary open-angle glaucoma is characterized by the progressive degeneration of the optic nerve, with the high intraocular pressure (IOP) being one of the main risk factors. The human trabecular meshwork (HTM), specifically the juxtacanalicular tissue (JCT), is responsible for placing resistance to the aqueous humor (AH) outflow and the resulting IOP control. Currently, the lack of a proper in vitro JCT model and the complexity of three-dimensional models impede advances in understanding the relationship between AH outflow and HTM degeneration. Therefore, we design an in vitro JCT model using a polycaprolactone (PCL) nanofibrous scaffold, which supports cells to recapitulate the functional JCT morphology and allow the study of outflow physiology. Mechanical and morphological characterizations of the electrospun membranes were performed, and human trabecular meshwork cells were seeded over the scaffolds. The engineered JCT was characterized by scanning electron microscopy, quantitative real-time polymerase chain reaction, and immunochemistry assays staining HTM cell markers and proteins. A pressure-sensitive perfusion system was constructed and used for the investigation of the outflow facility of the polymeric scaffold treated with dexamethasone (a glucocorticoid) and netarsudil (a novel IOP lowering the rho inhibitor). Cells in the in vitro model exhibited an HTM-like morphology, expression of myocilin, fibronectin, and collagen IV, genetic expression, outflow characteristics, and drug responsiveness. Altogether, the present work develops an in vitro JCT model to better understand HTM cell biology and the relationship between the AH outflow and the HTM and allow further drug screening of pharmacological agents that affect the trabecular outflow facility.

show abstract

Elevated Intraocular Pressure induces Ultrastructural Changes in the Trabecular Meshwork

Cited by 8 publications

References 31 publications

Light Microscopic Studies on the Morphology of Tissues Embedded in Epoxy Resin

Light Microscopic Studies on the Morphology of Tissues Embedded in Epoxy Resin

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

Nanofibrous PCL-Based Human Trabecular Meshwork for Aqueous Humor Outflow Studies

Contact Info

Product

Resources

About