MicroRNA profile of extracellular vesicles released by Müller glial cells

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 18, 2024

Introduction As with any other radial glia in the central nervous system, Müller derive from same neuroepithelial precursors, perform similar functions, and exhibit neurogenic properties as brain. glial cells retain progenitor-like characteristics adult human eye can partially restore visual function upon intravitreal transplantation into animal models of glaucoma. Recently, it has been demonstrated that intracellular communication is possible via secretion nano-sized membrane-bound extracellular vesicles (EV), which contain bioactive molecules like microRNA (miRNA) proteins induce phenotypic changes when internalised by recipient cells. Methods We conducted high-throughput sequencing to profile signature EV populations secreted culture used bioinformatics tools evaluate their potential role neuroprotective signalling attributed these Results Sequencing miRNA within suggested enrichment species associated stem such miR-21 miR-16, well previously found play a diverse cell functions retina: miR-9, miR-125b, let-7 family. A total 51 miRNAs were be differentially enriched compared whole originated. Bioinformatics analyses also indicated preferential was regulate genes involved proliferation survival, including PTEN, master inhibitor PI3K/AKT pathway. Discussion The results suggest release miRNA-enriched abundant anti-apoptotic networks likely represent significant proportion effect observed after retinal ganglion (RGC) depletion. Future studies will seek modulation putative activation pathways vitro vivo following internalisation Müller-EV target neurons.

Language: Английский

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Molecular Mechanisms of Vitamin E in Ocular Neurodegenerative Disorders: An Update on the Emerging Evidence and Therapeutic Implications

Journal of Ocular Pharmacology and Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Vitamin E is renowned for its potent antioxidant properties, crucial shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due pivotal role preserving cell membrane integrity combating cellular While importance overall health, neurodegeneration, acknowledged, the specific correlation between deficiency distinct ocular disorders need be further explored. This review delves into molecular mechanisms of disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, cataracts, emphasising therapeutic implications drawn from existing evidence. Relationship widely researched on, with primary protective attributed anti-inflammatory properties. However, studies on supplementation among human subjects present mixed results, suggesting complexities variability depending factors such as disorder, disease stage, genetic differences, form utilized. In conclusion, while holds promise mitigating neurodegeneration through supplementation's efficacy remains nuanced context dependent. More research works are essential elucidate precise potential disorders.

Language: Английский

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Assessment of Brain-Derived Neurotrophic Factor on Retinal Structure and Visual Function in Rodent Models of Optic Nerve Crush

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 798 - 798

Published: June 18, 2024

The effects of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival and visual function were assessed in rat mouse models optic nerve (ON) crush. ONs crushed Day 1, followed by intravitreal injections a vehicle or BDNF Days 1 8. spatial frequency threshold was measured using optokinetic tracking 7 14. On 15, complex (GCC) thickness quantified optical coherence tomography. Furthermore, all eyes enucleated for immunohistochemical analysis the surviving RGC somas axons. significantly reduced soma mice increased GCC intact eyes, with apparent axonal swelling both species. It displayed greater ON injury, moderately thicker bundles species rats. Visual ON-crushed animals, regardless treatment. Thus, we obtained comprehensive structural functional impact two rodent models. Our results provide foundation further evaluation design preclinical studies neuroprotectants as reference positive control.

Language: Английский

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Novel therapeutic targets for primary open-angle glaucoma identified through multicenter proteome-wide mendelian randomization

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 16, 2024

Background This study aimed to identify novel therapeutic targets for primary open-angle glaucoma (POAG). Methods The summary-data-based Mendelian randomization (SMR) method was used evaluate the genetic association between plasma proteins and POAG. Two sets of protein quantitative trait loci (pQTLs) data considered exposures were obtained from Icelandic Decoding Genetics Study UK Biobank Pharma Proteomics Project. summary-level genome-wide studies POAG extracted latest Round 10 release FinnGen consortium (8,530 cases 391,275 controls) (4,737 458,196 controls). Colocalization analysis screen out pQTLs that share same variant with as drug identified. two-sample randomization, reverse causality testing phenotype scanning performed further validate main findings. Protein-protein interaction, pathway enrichment druggability assessment conducted determine whether identified have potential targets. Results After systematic analysis, this eight circulating Three causal strong evidence colocalization, ROBO1 (OR = 1.38, p 1.48 × −4 , PPH4 0.865), FOXO3 0.35, 4.34 −3 0.796), ITIH3 0.89, 2.76 0.767), tier one Five medium support NCR1 1.25, 4.18 0.682), NID1 1.54 0.664), TIMP3 0.91, 4.01 −5 0.659), SERPINF1 0.81, 2.77 0.59), OXT 1.17, 9.51 0.526), classified two Additional sensitivity analyses validated robustness directionality these According assessment, Pimagedine, Resveratrol, Syringaresinol Clozapine may potentially be important in development new anti-glaucoma agents. Conclusion Our integrated associated These play roles neuroprotection, extracellular matrix regulation oxidative stress. Therefore, they promising combat

Language: Английский

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Identification of mutation of MYOC (c.1099G>A), a pedigree pathogenic gene of juvenile open angle glaucoma (JOAG): A case report

Medicine, Journal Year: 2024, Volume and Issue: 103(47), P. e40555 - e40555

Published: Nov. 22, 2024

Rationale: The MYOC gene is associated with juvenile open-angle glaucoma (JOAG). This study aims to provide genetic counseling for a Chinese JOAG family by detecting mutations identify high-risk individuals early intervention. It also supplements the clinical characteristics of patients mutations. Patient concerns: A 43-year-old presented sought medical attention in local hospital due 6-month decline binocular vision. He was diagnosed as and underwent surgery. patient had 11 members history JOAG. Diagnoses: After sequencing polymerase chain reaction products patient, c.1099 G > (p.G367R) mutation observed. That consistent diagnosis Intervention: Polymerase analyses 9 42 healthy were performed explore potential familial Outcomes: assisted diagnosing III-5 proband. Genetic detection indicated that exposed novel heterozygous missense (c.1099 [p.G367R]). co-segregation this trait observed pedigree verified. All 10 participants exhibiting phenotypes, whereas other did not show mutation. In terms (p.G367R), occurred when 1099th nucleotide encoding zone changed from A. Moreover, 367th amino acid coded base got mutated glycine arginine. DNAMAN sequence homology results showed residues MYOC: 367 significantly conserved among different species. addition, 3D protein conformation predicted these could decrease stability. Lessons: identified pathogenic pedigree. addition mutant spectrum population facilitates complete understanding molecular pathogenesis MYOC.

Language: Английский

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Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12802 - 12802

Published: Nov. 28, 2024

Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise Mediterranean diet can alleviate In this work, we first time estimated phylostratigraphic age indices (PAIs) all 153 POAG-related human genes in NCBI Gene Database. allowed us separate them into two groups: that appeared before after phylum Chordata, is, ophthalmologically speaking, camera-type eye evolved. Next, genes’ promoters, silico predicted 3835 candidate SNP markers significantly change TATA-binding protein (TBP) affinity these promoters and, through molecular mechanism, expression levels genes. Finally, verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, GeneMANIA—as well as ClinVar database. It was concluded POAG likely be a symptom self-domestication syndrome, downside being civilized.

Language: Английский

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