Mechanisms contributing to inhibition of retinal ganglion cell death by cell permeable peptain-1 under glaucomatous stress DOI Creative Commons
Gretchen A. Johnson, Bindu Kodati, Rooban B. Nahomi

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: June 28, 2024

Abstract This study assesses the neuroprotective potential of CPP-P1, a conjugate an anti-apoptotic peptain-1 (P1) and cell-penetrating peptide (CPP) in vitro, vivo, ex vivo glaucoma models. Primary retinal ganglion cells (RGCs) were subjected to either neurotrophic factor (NF) deprivation for 48 h or endothelin-3 (ET-3) treatment 24 received CPP-P1 vehicle. RGC survival was analyzed using Live/Dead assay. Axotomized human explants treated with vehicle seven days, stained marker RBPMS, analyzed. Brown Norway (BN) rats elevated intraocular pressure (IOP) weekly intravitreal injections six weeks. function evaluated pattern electroretinogram (PERG). axonal damage also assessed. RGCs from ocular hypertensive days isolated transcriptomic analysis. NF used qPCR target confirmation. led significant loss RGCs, which markedly reduced by treatment. decreased ET-3-mediated death. In explants, loss. IOP elevation resulted mid-peripheral peripheral retinas compared that naive rats, significantly PERG amplitude decline IOP-elevated mitigated Following BN analysis showed over 6,000 differentially expressed genes group vehicle-treated group. Upregulated pathways included CREB signaling synaptogenesis. A increase Creb1 mRNA phosphorylated Creb observed CPP-P1-treated RGCs. Our is through enhancement several settings mimic glaucomatous conditions. The findings this are as they address pressing need development efficacious therapeutic strategies maintain viability functionality associated glaucoma.

Language: Английский

Central nervous system regeneration DOI Creative Commons
Supraja G. Varadarajan, John L. Hunyara, Natalie R. Hamilton

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(1), P. 77 - 94

Published: Jan. 1, 2022

Language: Английский

Citations

166
Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells DOI Creative Commons
Feng Tian, Yuyan Cheng, Songlin Zhou

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2607 - 2624.e8

Published: June 28, 2022

Language: Английский

Citations

90
Drug in Drug: Quorum Sensing Inhibitor in Star-Shaped Antibacterial Polypeptides for Inhibiting and Eradicating Corneal Bacterial Biofilms DOI

Zhouyu Lu,

Wenjie Fan, Yang Ye

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Biofilm-related bacterial keratitis is a severe ocular infection that can result in drastic vision impairment and even blindness. However, the therapeutic efficiency of clinical antibiotic eyedrops often compromised because bacteria biofilms resist bactericide

Language: Английский

Citations

2
Gene therapy strategies for glaucoma from IOP reduction to retinal neuroprotection: Progress towards non-viral systems DOI

Antoine M. Hakim,

Benjamin Guido,

Lokesh Narsineni

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 196, P. 114781 - 114781

Published: March 20, 2023

Language: Английский

Citations

32
FABP5 regulates ROS‐NLRP3 inflammasome in glutamate‐induced retinal excitotoxic glaucomatous model DOI Open Access

Zhou Zeng,

Mengling You,

Cong Fan

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 10, 2025

Abstract Fatty acid binding proteins (FABPs) are a class of small molecular mass intracellular lipid chaperone that bind to hydrophobic ligands, such as long‐chain fatty acids. FABP5 expression was significantly upregulated in the N ‐methyl‐ d ‐aspartic (NMDA) model, microbead‐induced chronic glaucoma and DBA/2J mice. Previous studies have demonstrated can mediate mitochondrial dysfunction oxidative stress ischemic neurons, but role cell death retina NMDA injury models is unclear. In this study, we found altered model glutamate excitotoxicity regulated by Stat3. Inhibition alleviated imbalance activation NLRP3 inflammasome, reduced release inflammatory factors, ultimately attenuated excitotoxicity‐induced retinal ganglion loss. Meanwhile, caspase1 inhibitors could alleviate loss induced excitotoxicity. conclusion, inhibition protects cells from excitotoxic damage suppressing ROS‐NLRP3 inflammasome pathway. maybe promising new target for diagnosis treatment.

Language: Английский

Citations

1
The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection DOI
Irving Estevez,

Benjamin D. Buckley,

Marissa Lindman

et al.

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Resveratrol ameliorates polycystic ovary syndrome via transzonal projections within oocyte-granulosa cell communication DOI Creative Commons
Mingyue Chen, Chengyong He, Kongyang Zhu

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 12(2), P. 782 - 795

Published: Dec. 15, 2021

Rationale: Polycystic ovary syndrome (PCOS) is closely linked to follicular dysplasia and impaired bidirectional oocyte-granulosa cell (GC) communication. Given that PCOS a heterogeneous, multifactorial endocrine disorder, it important clarify the pathophysiology of this ovarian disease identify specific treatment. Methods: We generated rat models based on neonatal tributyltin (TBT) exposure studied therapeutic effect mechanism resveratrol (RSV), natural plant polyphenol. Transcriptome analysis was conducted screen significantly changed pathways, series experiments, such as quantitative real-time polymerase chain reaction (PCR), Western blot phalloidin staining, were performed in ovaries. also observed similar changes human samples using Gene Expression Omnibus (GEO) database PCR. Results: first found injury transzonal projections (TZPs), which are specialized filopodia mediate oocyte-GC communication follicles, may play an role etiology PCOS. successfully established TBT overexpressed calcium-/calmodulin-dependent protein kinase II beta (CaMKIIβ) inhibited TZP assembly. In addition, disruption CAMK2B upregulation from patients. Moreover, we demonstrated RSV potently ameliorated failure estrus cycle disorder through recovery via increased cytoplasmic calcium levels excessive phosphorylation CaMKIIβ. Conclusions: Our data indicated CaMKIIβ critical regulating assembly be involved pathogenesis associated with dysfunction. Investigation TZPs potent activators provides new insight target for PCOS, helpful improving female reproduction.

Language: Английский

Citations

55
Aging Effects on Optic Nerve Neurodegeneration DOI Open Access
Janet Coleman-Belin, Alon Harris, Bo Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2573 - 2573

Published: Jan. 29, 2023

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding mechanisms of changes can facilitate targeted treatments that arise at any point in life. In this review, we examine these age-related, neurodegenerative nerve, contextualize from anatomic molecular level, and appreciate their relationship with pathophysiology. From simple structural mechanical nerve head (ONH), epigenetic biochemical alterations tissue environment, multiple age-dependent drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, lowered regenerative ability respective axons. conjunction, aging decreases myelin preserve maximal conductivity, even “successfully” regenerated Glial cells, however, regeneratively overcompensate result a microenvironment promotes RGC axonal death. Better elucidating neurodegeneration remains interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, astrocytes; clarifying exact processes aged connective ultrastructural impacts; developing novel technologies pharmacotherapies target known genetic, biochemical, matrisome, neuroinflammatory markers. Management models should account when addressing glaucoma, diabetic retinopathy, other blinding diseases.

Language: Английский

Citations

17
The concept of gene therapy for glaucoma DOI Creative Commons

Robert Sulak,

Xiaonan Liu, Adrian Smędowski

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(1), P. 92 - 99

Published: May 25, 2023

Gene therapies, despite of being a relatively new therapeutic approach, have potential to become an important alternative current treatment strategies in glaucoma. Since glaucoma is not considered single gene disease, the identified goals therapy would be rather provide neuroprotection retinal ganglion cells, especially, intraocular-pressure-independent manner. The most commonly reported type vector for delivery studies adeno-associated virus serotype 2 that has high tropism resulting long-term expression and low immunogenic profile. recruit inducible genetic animal models optic neuropathy, like DBA/2J mice model high-tension nerve crush-model. Reported therapy-based cells targeting specific genes translating growth factors (i.e., brain derived neurotrophic factor, its receptor TrkB), regulation apoptosis neurodegeneration Bcl-xl, Xiap, FAS system, nicotinamide mononucleotide adenylyl transferase 2, Digit3 Sarm1), immunomodulation Crry, C3 complement), modulation neuroinflammation erythropoietin), reduction excitotoxicity CamKIIα) transcription Max, Nrf2). On other hand, some focus on lowering intraocular pressure, by impacting involved both, decreasing aqueous humor production aquaporin 1), increasing outflow facility COX2, prostaglandin F2α receptor, RhoA/RhoA kinase signaling pathway, MMP1, Myocilin). goal this review summarize state-of-art direction development glaucomatous neuropathy.

Language: Английский

Citations

17
Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2 DOI
Desheng Li, Yang Liu, Changzhu Li

et al.

Circulation, Journal Year: 2024, Volume and Issue: 150(2), P. 111 - 127

Published: May 10, 2024

G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is novel ligand of galanin (GALRs). In this study, we investigated the regulation spexin and GALRs on AF underlying mechanisms.

Language: Английский

Citations

7