Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage

Life Science Alliance, Journal Year: 2023, Volume and Issue: 6(8), P. e202301976 - e202301976

Published: May 9, 2023

Glaucoma is a common neurodegenerative disorder characterized by retinal ganglion cell death, astrocyte reactivity in the optic nerve, and vision loss. Currently, lowering intraocular pressure (IOP) first-line treatment, but adjuvant neuroprotective approaches would be welcome. Vitamin C possesses activities that are thought to related its properties as co-factor of enzymes antioxidant effects. Here, we show vitamin promotes phenotype increases gene expression neurotropic factors, phagocytosis, mitochondrial ATP production. This effect dependent on up-regulation secreted phosphoprotein 1 (SPP1) reactive astrocytes via transcription factor E2F1. SPP1+ turn promote survival mouse model glaucoma. In addition, oral administration lowers IOP mice. study identifies an additional pathway for suggests potential therapeutic role diseases such

Language: Английский

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Mechanisms contributing to inhibition of retinal ganglion cell death by cell permeable peptain-1 under glaucomatous stress

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

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Genetic and pharmacological correction of impaired mitophagy in retinal ganglion cells rescues glaucomatous neurodegeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Progressive loss of retinal ganglion cells (RGCs) and degeneration optic nerve axons are the pathological hallmarks glaucoma. Ocular hypertension (OHT) mitochondrial dysfunction linked to neurodegeneration vision in However, exact mechanism leading glaucomatous is poorly understood. Using multiple mouse models OHT human eyes from normal glaucoma donors, we show that induces impaired mitophagy RGCs, resulting accumulation dysfunctional mitochondria contributing neurodegeneration. reporter mice, precedes Notably, pharmacological rescue via Torin-2 or genetic upregulation RGC-specific Parkin expression restores structural functional integrity RGCs their ex-vivo retinal-explant cultures. Our study indicates contributes oxidative stress, Enhancing represents a promising therapeutic strategy prevent

Language: Английский

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Investigation of dental health and salivary microbiota characteristics of children with visual impairment in Guangzhou, China

BMC Oral Health, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 19, 2025

The prevalence of visual impairment (VS) among children in China is increasing. oral microbiome crucial for maintaining homeostasis and health. This study aimed to investigate the health hygiene habits with VS Guangzhou explore differences salivary microbiota (SM) between healthy vision (HS). included examinations surveys 101 VS. Saliva samples from 20 HS were analysed microbiota. 16s rRNA V3-V4 regions sequenced using Illumina MiSeq platform operational taxonomic units clustered QIIME statistical analysis. Inadequate was observed VS, aged 6–16, who displayed a high caries rate 92.1%. There no significant difference overall composition two groups. group had higher abundance Bacillota, Patescibacteria, Spirochaetota at phylum level; Bacilli, Negativicutes, Saccharimonadia class Streptococcus genus level. In contrast, showed greater Actinomycetota, Bacteroidota, Pseudomonadota, Fusobacteriota (at level) Actinomycetia, Bacteroidia, Gammaproteobacteria, Fusobacteriia, Clostridia level), along Rothia, Neisseria, Veillonella, Prevotella_7, Actinomyces, Leptotrichia, Lactobacillales level). Actinomycetota significantly positively correlated gingivitis dental caries, salivarius more abundant underscores importance improving healthcare schoolchildren Guangzhou, provides valuable insights into characteristics this population, identifying potential targets interventions enhancing

Language: Английский

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Modulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11557 - 11557

Published: July 17, 2023

Oxidative stress (OS)-induced mitochondrial damage is a risk factor for primary open-angle glaucoma (POAG). Mitochondria-targeted novel antioxidant therapies could unearth promising drug candidates the management of POAG. Previously, our dual-acting hybrid molecule SA-2 with nitric oxide-donating and activity reduced intraocular pressure improved aqueous humor outflow in rodent eyes. Here, we examined mechanistic role trabecular meshwork (TM) cells vitro measured intracellular enzymes during OS. Primary human TM isolated from normal (hNTM) or glaucomatous (hGTM) post-mortem donors transformed (GTM-3) were used assays. We effect on oxygen consumption rate (OCR) extracellular acidification (ECAR) using Seahorse Analyzer without oxidant, tert-butyl hydroperoxide (TBHP) treatment. Concentrations total enzymes, catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx) measured. observed significant protection both hNTM hGTM TBHP-induced cell death by SA-2. Antioxidant elevated SA-2-treated compared to TBHP-treated cells. In addition, demonstrated an increase metabolic parameters. Altogether, protected OS via increasing energy parameters enzymes.

Language: Английский

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Therapeutic Potential of Antioxidants and Hybrid TEMPOL Derivatives in Ocular Neurodegenerative Diseases: A Glimpse into the Future

Biomedicines, Journal Year: 2023, Volume and Issue: 11(11), P. 2959 - 2959

Published: Nov. 1, 2023

Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ischemic stroke. Increased oxidative stress accumulation ROS have been implicated progression these diseases. As result, there has growing interest exploring potential therapeutic prophylactic strategies involving exogenous antioxidants. In recent years, advancements development synthetic antioxidants for targeting reactive (ROS) One area focus hybrid TEMPOL derivatives. context diseases, application next-generation may offer new avenues neuroprotection. By reducing retina optic nerve, compounds to preserve retinal ganglion cells trabecular meshwork protect against nerve damage, mitigating irreversible blindness associated with This review seeks highlight impact their derivatives on disorders.

Language: Английский

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Mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in glaucomatous retinal ganglion cell degeneration—a mini review

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: May 12, 2023

Glaucoma is a leading cause of blindness worldwide, commonly associated with elevated intraocular pressure (IOP), to degeneration the optic nerve and death retinal ganglion cells, output neurons in eye. In recent years, many studies have implicated mitochondrial dysfunction as crucial player glaucomatous neurodegeneration. Mitochondrial function has been an increasingly researched topic glaucoma, given its vital role bioenergetics propagation action potentials. One most metabolically active tissues body characterized by high oxygen consumption retina, particularly cells (RGCs). RGCs, which long axons that extend from eyes brain, rely heavily on energy generated oxidative phosphorylation for signal transduction, rendering them more vulnerable damage. various glaucoma models, stress protein aggregates endoplasmic reticulum (ER) observed RGCs. However, it shown two organelles are connected through network called mitochondria-associated ER membranes (MAMs); hence this crosstalk pathophysiological condition such should be evaluated. Here, we review current literature suggestive related indicating potential cross-signaling roles MAMs.

Language: Английский

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Flow cytometric method for the detection and quantification of retinal cell death and oxidative stress

Experimental Eye Research, Journal Year: 2023, Volume and Issue: 233, P. 109563 - 109563

Published: June 29, 2023

Language: Английский

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Investigation of visually impaired schoolchildren's dental health and salivary microbiota characteristics in Guangzhou, China

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

Published: July 16, 2024

Background Reports indicate that the prevalence of visual impairment (VS) among children in China is on rise. The oral microbiome plays an essential role maintaining homeostasis and health. primary objective was to examine health their hygiene habits VS Guangzhou. secondary explore differences saliva samples microbiota (SM) between HS (health children) children. Method 101 were chosen have examined surveyed. profiled from 20 healthy (HS) Guangzhou population, 16s rRNA V3-V4 region sequenced using Illumina MiSeq platform. operational taxonomic units (OTUs) clustered QIIME statistical analysis performed by R. Results Oral inadequate age 6-16, who exceptionally high caries rate 92.1%. There no statistically significant distinction observed composition salivary microbial community two groups. had a higher abundance Firmicutes, Patescibacteria, Spirochaetes at phylum level, Bacilli, Negativicutes, Saccharimonadia classes Streptococcus genus level. In contrast, more Actinobacteria, Bacteroidetes, Proteobacteria, Fusobacteriota Bacteroidia, Gammaproteobacteria, Fusobacteriia, Clostridia Rothia, Neisseria, Veillonella, Prevotella_7, Actinomyces, Leptotrichia, lactobacillales Notably, Actinobacteria significantly positively correlated with gingivitis dental caries. Additionally, salivarius, within substantially abundant Conclusion study highlights importance care for visually impaired schoolchildren It provides valuable insights into characteristics this population suggests potential targets intervention improve status.

Language: Английский

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