Bioengineering, Год журнала: 2024, Номер 12(1), С. 6 - 6
Опубликована: Дек. 25, 2024
Glaucoma, a progressive and multifactorial optic neurodegenerative disease, still poses significant challenges in both diagnosis management remains perpetual enigma [...].
Язык: Английский
Aging and Disease, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Age-related macular degeneration (AMD) is a prevalent degenerative disorder of the central retina, which holds global significance as fourth leading cause blindness. The condition characterized by multifaceted pathophysiology that involves aging, oxidative stress, inflammation, vascular dysfunction, and complement activation. complex interplay these factors contributes to initiation progression AMD. Current treatments primarily address choroidal neovascularization (CNV) in neovascular However, approval novel drug therapies for atrophic more gradual variant, known geographic atrophy (GA), has recently occurred. In light substantial impact AMD on affected individuals' quality life strain it places healthcare systems, there pressing need innovative medications. This paper aims provide an updated comprehensive overview advancements our understanding etiopathogenesis Special attention will be given influence aging altered redox status mitochondrial dynamics, cell death pathways, intricate between stress system, specifically context GA. Additionally, this review shed newly approved explore emerging alternative treatment strategies field. objective contribute ongoing dialogue surrounding AMD, offering insights into latest developments may pave way effective management intervention approaches.
Язык: Английский
Процитировано
13
BMJ Open Ophthalmology, Год журнала: 2025, Номер 10(1), С. e002103 - e002103
Опубликована: Март 1, 2025
Background Glaucoma, a leading cause of irreversible blindness worldwide, is characterised by retinal ganglion cell degeneration. Increasing evidence points to metabolic dysfunction, particularly mitochondrial as contributing factor glaucomatous neurodegeneration. This systematic review and meta-analysis aimed identify key pathways biomarkers associated with primary open-angle glaucoma (POAG). Methods A literature search was conducted studies measuring metabolites in plasma aqueous humour from patients POAG using metabolomics techniques. Enrichment analyses for significantly increased were MetaboAnalyst. Meta-analyses performed random-effects models calculate effect sizes reported at least three studies. Results 17 involving included. Pathway analysis revealed significant enrichment the arginine proline metabolism pathway both plasma. Additionally, phenylalanine enriched These are oxidative stress neurodegeneration, which factors pathology. Meta-analysis identified several elevated metabolites, including lysine, glutamine, alanine, histidine, carnitine creatinine humour, well methionine Conclusions study underscores central role dysfunction POAG, highlighting specific that could serve early diagnosis therapeutic intervention. Future research should prioritise longitudinal untargeted metabolomic profiling further deepen our understanding changes their contributions progression. PROSPERO registration number CRD42024512098.
Язык: Английский
Процитировано
1
Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1193 - 1193
Опубликована: Авг. 22, 2023
Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping the optic disc, and typical pattern visual field defects, is leading cause severe impairment blindness worldwide. Elevated intraocular pressure (IOP) risk factor for glaucoma development. However, can also develop at normal levels. An increased susceptibility cells to IOP, systemic vascular dysregulation, endothelial dysfunction, autoimmune imbalances have been suggested as playing role in pathophysiology normal-tension glaucoma. Since inflammation oxidative stress play all forms glaucoma, goal this review article present an overview inflammatory pro-oxidant mechanisms discuss immunomodulatory antioxidant treatment approaches.
Язык: Английский
Процитировано
15
International Journal of Ophthalmology, Год журнала: 2024, Номер 17(4), С. 638 - 645
Опубликована: Март 26, 2024
AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage N-methyl-D-aspartate (NMDA)-induced retinal ganglion (RGC) injury in a mouse model glaucoma. METHODS: The effects rat R28 precursor line were assessed using counting kit-8 assays Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured fluorescent probe 2'-7'-dichlorofluorescin diacetate flow cytometry. role NMDA-induced RGC glaucoma determined by immunostaining frozen sections retina. metabolome retina mice with evaluated liquid chromatography-mass spectroscopy (LC-MS) untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated to cells vitro. also protected RGCs against model. Untargeted analyses showed that increased multiple metabolites, including L-arginine L-carnitine, CONCLUSION: has properties an vitro vivo through modulation and/or L-carnitine metabolism.
Язык: Английский
Процитировано
5
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8876 - 8876
Опубликована: Авг. 15, 2024
Glaucoma, a leading cause of blindness, is multifactorial condition that leads to progressive loss retinal ganglion cells (RGCs) and vision. Therapeutic interventions based on reducing ocular hypertension are not always successful. Emerging features glaucoma include mitochondrial dysfunction oxidative stress. In the current study, NDI1-based gene therapy, which improves function reduces reactive oxygen species, was delivered intraocularly via an adeno-associated viral vector (AAV). This AAV-NDI1 therapy protected RGCs from cell death in treated (1552.4 ± 994.0 RGCs/mm2) versus control eyes (1184.4 978.4 RGCs/mm2, p < 0.05) aged DBA/2J mice, murine model glaucoma. The photonegative responses (PhNRs) were also improved (6.4 3.3 µV) (5.0 3.1 µV, these mice. provided benefits glaucomatous human lamina cribrosa (LC) by significantly increasing basal maximal consumption rates ATP production cells. Similarly, NDI1 H2O2-insulted primary porcine LC study highlights potential utility therapies improving treatment
Язык: Английский
Процитировано
4
Cells, Год журнала: 2023, Номер 12(15), С. 1969 - 1969
Опубликована: Июль 30, 2023
This review aims to provide a better understanding of the emerging role mitophagy in glaucomatous neurodegeneration, which is primary cause irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated pathogenesis glaucoma various populations. The association between polymorphisms these increased risk presented. Reduction intraocular pressure (IOP) currently only modifiable factor for glaucoma, while clinical trials highlight inadequacy IOP-lowering therapeutic approaches prevent sight loss many patients. Mitochondrial dysfunction thought increase susceptibility retinal ganglion cells (RGCs) factors degeneration. Mitophagy holds vital mitochondrial quality control processes, current explores pathways may be linked their potential.
Язык: Английский
Процитировано
9
Eye, Год журнала: 2024, Номер 38(13), С. 2497 - 2498
Опубликована: Апрель 18, 2024
Язык: Английский
Процитировано
3
PLoS ONE, Год журнала: 2024, Номер 19(7), С. e0307227 - e0307227
Опубликована: Июль 11, 2024
Primary open angle glaucoma is a leading cause of visual impairment and blindness which commonly treated with drugs or laser but may require surgery. Tenon’s ocular fibroblasts are involved in wound-healing after filtration surgery compromise favourable outcome by contributing to fibrosis. To investigate changes gene expression key pathways the glaucomatous state we performed genome-wide RNA sequencing. Human were cultured from normal human donors undergoing eye (n = 12). mRNA was extracted RNA-Seq on Illumina platform. Differentially expressed genes identified using bioinformatics pipeline consisting FastQC, STAR, FeatureCounts edgeR. Changes biological functions determined Enrichr clustered Cytoscape. A total 5817 differentially between versus eyes. Enrichment analysis showed 787 significantly different into 176 clusters. eyes signs fibrosis fibroblast myofibroblast transdifferentiation associated mitochondrial fission, remodeling extracellular matrix, proliferation, unfolded protein response, inflammation apoptosis relate pathogenesis detrimental effects topical therapies. Altered contribute an unfavourable This work presents transcriptome identify therapeutic value improve surgical outcomes.
Язык: Английский
Процитировано
3
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Since the trabecular meshwork (TM) is central to intraocular pressure (IOP) regulation and glaucoma, a deeper understanding of its genomic landscape needed. We present multimodal, single-cell resolution analysis mouse limbal cells (includes TM). In total, we sequenced 9,394 wild-type TM cell transcriptomes. discovered three subtypes with characteristic signature genes validated by immunofluorescence on tissue sections whole-mounts. The are robust, being detected in datasets for two diverse strains independent data from institutions. Results show compartmentalized enrichment critical pathways specific subtypes. Distinctive signatures include increased expression responsible 1) extracellular matrix structure metabolism (TM1 subtype), 2) secreted ligand signaling support Schlemm's canal (TM2), 3) contractile mitochondrial/metabolic activity (TM3). ATAC-sequencing identified active transcription factors cells, including LMX1B. Mutations LMX1B cause high IOP glaucoma. emerging as key factor normal mitochondrial function much higher TM3 than other cells. To understand role Lmx1b V265D/+ mutant mice. mice, were uniquely affected pronounced pathway changes. This supports primary dysfunction within initiating elevation that causes glaucoma these Importantly, treatment vitamin B 3 (nicotinamide), enhance metabolic resilience, significantly protected mice elevation.
Язык: Английский
Процитировано
3
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Март 20, 2025
Retinal cell apoptosis is the primary pathological process in many retinal diseases, including retinitis pigmentosa and age-related macular degeneration, which can cause severe visual impairment blindness. Lycium barbarum L. , a traditional Chinese medicinal botanical drug, has long history extensive application ophthalmic disease prevention treatment. This study systematically reviewed key active metabolites L., polysaccharides, carotenoids, flavonoids, that exert protective effects. A comprehensive analysis of pharmacological effects underlying molecular mechanisms its treatment apoptosis, essential aspects such as antioxidant activity, anti-inflammatory properties, autophagy regulation, mitochondrial function preservation, to establish solid theoretical basis for further investigation value ophthalmology provide reference future research directions.
Язык: Английский
Процитировано
0