DAMPs and DAMP-sensing receptors in inflammation and diseases

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 752 - 771

Published: April 1, 2024

Language: Английский

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Therapeutic effects of tetrahedral framework nucleic acids and tFNAs‐miR22 on retinal ischemia/reperfusion injury

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(11)

Published: July 31, 2024

Abstract Retinal ischemia/reperfusion injury (RI/R) is a common pathological process in ophthalmic diseases, which can cause severe visual impairment. The mechanisms underlying RI/R damage and repair are still unclear. Scholars actively exploring effective intervention strategies to restore impaired function. With the development of nucleic acid nanomaterials, tetrahedral framework acids (tFNAs) have shown promising therapeutic potential various fields such as stem cells, biosensors, tumour treatment due their excellent biological properties. Besides, miRNA‐22‐3p (miR‐22), an important regulatory factor neural tissue, has been proven positive effects neurodegenerative diseases. By stably constructing complex miR22 (tFNAs‐miR22), we observed that tFNAs‐miR22 had effect on retinal tissue. Previous studies tFNAs effectively deliver miR‐22 into damaged neurons, subsequently exerting neuroprotective effects. Interestingly, found there was certain synergistic between miR‐22. selectively activated ERK1/2 signalling pathway reduce neuronal apoptosis, accelerate cell proliferation, synaptic functional activity. In this study, established simple yet small molecule drug for may become neuroprotectant treating type vision impairment disease future.

Language: Английский

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TGFβ2 alters segmental outflow and ECM ultrastructure in the trabecular meshwork

Experimental Eye Research, Journal Year: 2025, Volume and Issue: 255, P. 110377 - 110377

Published: April 10, 2025

Language: Английский

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Stop codon variant in EFEMP1 is associated with primary open-angle glaucoma due to impaired regulation of aqueous humor outflow

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 241, P. 109859 - 109859

Published: March 11, 2024

Language: Английский

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The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Sept. 4, 2024

The retina is a highly heterogeneous tissue, both cell-wise but also regarding its extracellular matrix (ECM). stiffness of the ECM pivotal in retinal development and maturation has been associated with onset and/or progression numerous pathologies, such as glaucoma, proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), epiretinal membrane (ERM) formation or uveitis. Nonetheless, much remains unknown about biomechanical milieu retina, specifically role that Müller glia play principal mechanosensors major producers constituents. So far, new approaches need to be developed further knowledge field mechanobiology for ECM-target applications arise. In this review, we focus on involvement shaping altering under physiological pathological conditions look into various biomaterial options more accurately replicate impact

Language: Английский

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An Autotaxin-Induced Ocular Hypertension Mouse Model Reflecting Physiological Aqueous Biomarker

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(2), P. 32 - 32

Published: Feb. 22, 2024

Purpose: Animal models of ocular hypertension (OH) have been developed to understand the pathogenesis glaucoma and facilitate drug discovery. However, many these are fraught with issues, including severe intraocular inflammation technical challenges. Lysophosphatidic acid (LPA) is implicated in trabecular meshwork fibrosis increased resistance aqueous outflow, factors that contribute high pressure (IOP) human open-angle glaucoma. We aimed elevate IOP by increasing expression LPA-producing enzyme autotaxin (ATX) mouse eyes. Methods: Tamoxifen-inducible ATX transgenic mice were developed. Tamoxifen was administered six- eight-week-old via eye drops achieve overexpression eye. retinal thickness measured over time, flat-mount evaluated count ganglion cells (RGCs) loss after three months. Results: Persistent elevation eyes confirmed through immunohistochemistry LysoPLD activity measurement. Tg exhibited significantly for nearly two months following tamoxifen treatment, no anterior segment changes or inflammation. Immunohistochemical analysis revealed enhanced extracellular matrix near angle weeks induction. This correlated reduced outflow facility, indicating sustained induces fibrosis, elevating IOP. Although inner layer remained stable, peripheral retina showed a notable reduction RGC cell count. Conclusions: These findings confirm successful creation an OH model, which prompts maintains elevated extended periods.

Language: Английский

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A20 Attenuates the Fibrotic Response in the Trabecular Meshwork

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(4), P. 1928 - 1928

Published: Feb. 9, 2022

Although the extracellular matrix (ECM) in trabecular meshwork (TM) cells is known to be important intraocular pressure (IOP) regulation, molecular mechanisms involved generating a glaucomatous environment TM are not completely understood. Recently we identified pathway, transforming growth factor beta 2 (TGFβ2)–toll-like receptor 4 (TLR4) signaling crosstalk, as an regulator of damage TM, which contributes fibrosis. Here evaluate novel target, A20, also tumor necrosis alpha-induced protein 3 (TNFAIP3), may help block pathological TGFβ2–TLR4 signaling. Primary human were analyzed for A20 message and fibronectin expression after treatment with TGFβ2. increased when TLR4 pathway was inhibited cells. In addition, TGFβ2, inducer fibrosis, expression, while at same time decreasing A20. We then overexpressed order test effect on lipopolysaccharide (LPS), or cellular extra domain A (cFN-EDA). Importantly, overexpression rescued fibrotic response treated LPS, cFN-EDA. situ hybridization used probe RNA age-matched control (C57BL/6J) mice that constitutively express EDA isoform (B6.EDA+/+). this mouse model glaucoma, versus cyclic manner 6 weeks 1 year age, but 8 months. Overall, these data suggest work through negative feedback mechanism attenuating ability induce

Language: Английский

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Role of integrins in the development of fibrosis in the trabecular meshwork

Frontiers in Ophthalmology, Journal Year: 2023, Volume and Issue: 3

Published: Oct. 24, 2023

Primary open angle glaucoma (POAG) is a progressive and chronic disease exhibiting many of the features fibrosis. The extracellular matrix (ECM) in trabecular meshwork (TM) undergoes extensive remodeling enhanced rigidity, resembling fibrotic changes. In addition, there are changes associated with myofibroblast activation cell contractility that further drives tissue fibrosis stiffening. This review discusses what known about integrins TM their involvement processes.

Language: Английский

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The Fibro-Inflammatory Response in the Glaucomatous Optic Nerve Head

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13240 - 13240

Published: Aug. 26, 2023

Glaucoma is a progressive disease and the leading cause of irreversible blindness. The limited therapeutics available are only able to manage common risk factor glaucoma, elevated intraocular pressure (IOP), indicating great need for understanding cellular mechanisms behind optic nerve head (ONH) damage during progression. Here we review known inflammatory fibrotic changes occurring in ONH. In addition, describe novel mechanism toll-like receptor 4 (TLR4) transforming growth beta-2 (TGFβ2) signaling crosstalk cells ONH that contribute glaucomatous damage. Understanding molecular within between can help identify new drug targets therapeutics.

Language: Английский

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scAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16253 - 16253

Published: Nov. 13, 2023

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment available restore nerve function. In this paper, we aimed develop a novel gene therapy for using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated therapeutic effects of vitro vivo dexamethasone (DEX)-induced models. found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA increased phosphor-cofilin Ser3 levels. scAAV2-Trx2-C3 was also shown inhibit oxidative stress, fibronectin expression, alpha-SMA DEX-treated cells. NeuN immunostaining TUNEL assay mouse tissues performed evaluate its neuroprotective effect upon RGCs, whereas changes were monitored via rebound tonometer. The present study showed can protect RGCs from degeneration reduce DEX-induced model glaucoma, while immunohistochemistry revealed decreased after transduction murine eye tissues. Our results suggest AAV2-Trx2-C3 modulates outflow resistance trabecular meshwork, protects other ocular damage, may lead development glaucoma.

Language: Английский

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