Pro‐Inflammatory Cytokines in Aqueous Humor From ADAMTS10‐Mutant Beagles at an Early Stage of Open‐Angle Glaucoma

Veterinary Ophthalmology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

ABSTRACT Objective To investigate the level of pro‐inflammatory cytokines in aqueous humor from ADAMTS10 ‐mutant research Beagles at an early stage open‐angle glaucoma (OAG). Animals Studied Twenty‐four were enrolled into this case‐controlled study. Three groups study: (1) Intraocular pressure (IOP) 15–25 mmHg (normotensive IOP), (2) IOP 25–30 mmHg, and (3) 30–36 mmHg. An unaffected control group that either ‐wildtype (WT) or heterozygote‐carrier with normotensive IOPs also enrolled. Procedures Aqueous samples collected analyzed for 16 using Canine Cytokine SpikeMix target mass spectrometry via multiple reaction monitoring (MRM‐MS). Statistical differences between four groups' cytokines, as well correlations IOPs, Kruskal‐Wallis tests Spearman's rho ( ρ ) correlations, respectively. Results n = 8); 6); 5); Control (WT 3, carrier 2, total 5). There no across (all p ‐values > 0.05). IL‐13 had a moderate positive correlation IOP, but was non‐significant 0.373, 0.073); IL‐1β negative −0.344, 0.100). All other only mild (| | < 0.229, Conclusions significant changes investigated elevated canine ‐OAG.

Language: Английский

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A Multi-Omics Study Reveals Molecular Characteristics and Therapeutic Targets of Salidroside in Reducing TGF-β2-Induced ECM Expression

Experimental Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 110386 - 110386

Published: April 1, 2025

Language: Английский

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Ambient Particulate Matter Exposure Increases the Risk of Suboptimal Outcomes of Glaucoma Surgery

Published: May 13, 2025

Purpose: Postoperative suboptimal outcome is a big challenge for patients undergoing conjunctival incision glaucoma surgery. This study aimed to investigate the association between particulate matter exposure and postoperative outcomes within different periods. Design: A retrospective, population-based cohort study. Participants: total of 6,141 who underwent conjunctiva surgeries from January 2015 December 2023. Methods: Patient data, including outcomes, demographics, medical surgical history were collected Eye Ear, Nose, Throat Hospital, Fudan University. Air pollution data obtained using bilinear interpolation. The relationship (PM) was analyzed survival analysis, Cox proportional hazards regression restricted cubic splines. combined effect level windows calculated during 20 100 days after Subgroup analyses assessed interaction effects. Main Outcome Measures: Hazard ratios (HRs) 95% confidence intervals (CIs) in relation an interquartile range (IQR) increase PM levels. Results: Individuals exposed higher levels showed more rapidly. Higher PMs significantly associated with increased cumulative first 90 surgery particularly, hazard 1.0731 (95%CI: 1.0334-1.1144) 1.0412 1.0160-1.0671) each 10 µg/m³ PM_2.5 PM₁₀, respectively. effects beyond threshold (60 PM_2.5, 80 PM₁₀) became significant over time. Male those aged < 60 years exhibited elevated risks adverse specifically 60- 90-day windows. robustness conclusion confirmed by sensitivity analyses. Conclusions: Ambient increases risk surgery, especially Given ubiquity ambient air pollution, proactive integration evaluation into planning care protocols may warrant consideration ophthalmic practice.

Language: Английский

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Proteomics Analyses of Small Extracellular Vesicles of Aqueous Humor: Identification and Validation of GAS6 and SPP1 as Glaucoma Markers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6995 - 6995

Published: June 26, 2024

Cataracts and glaucoma account for a high percentage of vision loss blindness worldwide. Small extracellular vesicles (sEVs) are released into different body fluids, including the eye's aqueous humor. Information about their proteome content characterization in ocular pathologies is not yet well established. In this study, humor sEVs from healthy individuals, cataracts, patients were studied, specific protein profiles characterized. Moreover, potential identified proteins as diagnostic biomarkers was evaluated. The patients' with cataracts compared to individuals analyzed by quantitative proteomics. Validation performed western blot (WB) ELISA. A total 828 peptides 192 quantified. After data analysis R program, 8 significantly dysregulated 16 showed an expression ratio ≥ 1.5. By WB ELISA using directly samples, dysregulation 9 mostly confirmed. Importantly, GAS6 SPP1 ability glaucoma, which combination allowed discriminating control area under curve 76.1% sensitivity 65.6% specificity 87.7%.

Language: Английский

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ATF4 regulates mitochondrial dysfunction, mitophagy, and autophagy, contributing to corneal endothelial apoptosis under chronic ER stress in Fuchs dystrophy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Abstract Purpose Endoplasmic reticulum (ER) stress, mitochondrial dysfunction, mitophagy/autophagy are known to contribute independently corneal endothelial (CE) apoptosis in Fuchs’ dystrophy (FECD). However, the role of a well-studied specific ER stress pathway (PERK-ATF4-CHOP) regulating mitophagy/autophagy, and is unknown. The purpose this study explore ATF4 dysfunction leading CEnC FECD. Methods Human cell line (HCEnC-21T), (F35T), primary human cells were treated with stressor tunicamycin (0.01, 0.1, 1, 10 μg/mL) for 24 and/or 48 hours. siRNA was used knock down 21T cells. Cell viability measured using an MTT assay (10 μg/mL hours). Mitochondrial bioenergetics analyzed by measuring mitochondria membrane potential (MMP) loss TMRE ATP production complex V kit at hours post tunicamycin. Mitochondrial-mediated intrinsic apoptotic proteins, mitophagy, autophagy marker proteins Western blotting +/- +/+ mice irradiated UVA assess pro-apoptotic death vivo . Results F35T had significantly increased expression molecules (eIF2α, ATF4, CHOP) mitochondrial-mediated (cleaved PARP, caspase 9, 3) along fragmentation compared baseline, which further after treatment also decreased knockdown attenuated molecules, rescued MMP loss, reduced downregulated altered/excessive Parkin-mediated mitophagy Akt/mTOR-mediated reduction caspases, cellular viability. ATF4+/-mice CE numbers improved morphology CHOP ATF4+/+ post-UVA. Conclusions Pro-apoptotic induction under tunicamycin-induced disrupts dynamics, activation excessive autophagy/mitophagy. ATF4-induced plays key switching apoptosis. This highlights importance ER-mitochondrial crosstalk its contribution

Language: Английский

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Congenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: 111(10), P. 2265 - 2282

Published: Sept. 17, 2024

Language: Английский

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Intravitreal AAV2 gene delivery to feline retinal ganglion cells

Vision Research, Journal Year: 2024, Volume and Issue: 226, P. 108519 - 108519

Published: Nov. 16, 2024

Effective strategies for the neuroprotection and preservation of retinal ganglion cells (RGCs) remain elusive in management glaucoma. A spontaneous genetic model glaucoma has been identified cats extensively characterized as a viable translational model, with eye size anatomy similar to humans. In this study we sought establish initial proof concept gene delivery feline RGCs via intravitreal injection AAV2 normal cats. Pre-retinal, posterior vitreal AAV2/2-CMV-GFP, was performed overlying area centralis 5 adult Immunosuppressive oral prednisolone administered perioperatively gradually tapered over 6-10wks post-injection. Ophthalmic examination pre- The GFP reporter expression morphological effects viral transduction on retina were monitored vivo using confocal scanning laser ophthalmoscopy (cSLO) optical coherence tomography (OCT), respectively (Spectralis OCT-HRA, Heidelberg), at 1-2wk intervals 6-10wks. Full-field electroretinograms (ERG) visual evoked potentials (VEP) recorded baseline Retinas examined by histology immunolabeling RGC marker RBPMS Müller cell astrocyte SOX9, retina, optic nerve (ON), tract lateral geniculate nucleus (LGN). GFP+ axons visualized cSLO 1-2 weeks No changes observed OCT but 3/5 eyes exhibited mild inflammation histology. Retinal ON function preserved injected compared untreated eyes. predominantly RBPMS+ well SOX9+ cells. fluorescence throughout fiber central pathway. Peak (up ∼ 20 %) regions high expression, < 1 % expressed across whole retina. Our data provide that pre-retinal AAV2/2 may represent feasible platform highlight need further refinement improve efficiency control low-grade inflammation.

Language: Английский

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Identification of Meibomian gland stem cell populations and mechanisms of aging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 10, 2024

Summary Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities niche of cells the signals controlling their activity are poorly defined. Using snRNA-seq, vivo lineage tracing, ex live imaging, genetic studies mice, we identified markers for populations that maintain distinct regions uncovered Hh signaling as key regulator proliferation. Consistent this, human carcinoma exhibited increased signaling. Aged displayed decreased EGF signaling, deficient innervation, loss collagen I fibroblasts, indicating alterations both glandular epithelial surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches treat aging-associated loss.

Language: Английский

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Effects of Telmisartan on Intraocular Pressure, Blood Pressure, and Ocular Perfusion Pressure in Normal and Glaucomatous Cats

Translational Vision Science & Technology, Journal Year: 2024, Volume and Issue: 13(9), P. 15 - 15

Published: Sept. 12, 2024

To determine the effect of telmisartan on intraocular pressure (IOP), blood (BP), and ocular perfusion (OPP) in normal glaucomatous cats.

Language: Английский

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Trabecular Meshwork Abnormalities in a Model of Congenital Glaucoma Due to LTBP2 Mutation

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(12), P. 28 - 28

Published: Oct. 21, 2024

To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation LTBP2.

Language: Английский

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