Advanced Glycation End-Products and Diabetic Neuropathy of the Retina

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2927 - 2927

Published: Feb. 2, 2023

Diabetic retinopathy is a tissue-specific neurovascular impairment of the retina in patients with both type 1 and 2 diabetes. Several pathological factors are involved progressive interdependence between cells that consist units (NVUs). The advanced glycation end-products (AGEs) one major cause impairments coupling diabetic retinopathy. Although exact mechanisms for toxicities AGEs have not been definitively determined, AGE-receptor AGE (RAGE) axis, production reactive oxygen species, inflammatory reactions, activation cell death pathways associated NVUs More specifically, neuronal an irreversible change directly vision reduction patients. Thus, neuroprotective therapies must be established therapeutic targets to examine ameliorate changes This review focuses on basic findings AGE-induced abnormalities potential approaches, including use anti-glycated drugs protect

Language: Английский

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A systematic review of inherited retinal dystrophies in Pakistan: updates from 1999 to April 2023

BMC Ophthalmology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 5, 2024

Abstract Background Inherited retinal degenerations (IRDs) are a group of rare genetic conditions affecting retina the eye that range in prevalence from 1 2000 to 4000 people globally. This review is based on retrospective analysis research articles reporting IRDs associated findings Pakistani families between 1999 and April 2023. Methods Articles were retrieved through survey online sources, notably, PubMed, Google Scholar, Web Science. Following stringent selection criterion, total 126 conference abstracts considered. All reported variants cross-checked validated for their correct genomic nomenclature using different resources/databases, pathogenicity scores explained as per ACMG guidelines. Results A 277 unique sequence 87 distinct genes, previously known cause IRDs, uncovered. In around 70% cases, parents index patient consanguineously married, approximately 88.81% detected found homozygous state. Overall, more than 95% cases recessively inherited. Missense predominant (41.88%), followed by Indels/frameshift (26.35%), nonsense (19.13%), splice site (12.27%) synonymous change (0.36%). Non-syndromic significantly higher syndromic (77.32% vs. 22.68%). Retinitis pigmentosa (RP) was most frequently observed IRD Leber’s congenital amaurosis (LCA). Altogether, mutations PDE6A gene leading TULP1 gene. Conclusion summary, notable expressing inherited monogenic disorders including likely due highest consanguinity country leads expression pathogenic

Language: Английский

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Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 201 - 201

Published: Feb. 4, 2024

Retinitis pigmentosa is a common cause of inherited blindness in adults, which many cases associated with an increase the formation reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown resveratrol (RSV) promising molecule can mitigate PARP1 overactivity, but its low bioavailability limitation for medical use. This study examined impact synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), 661W line against H2O2 oxidative stress rd10 mice. PIC-OCT possesses better ADME profile than RSV. In response H2O2, cells pretreated preserved viability more 38% by significantly promoting SIRT1 nuclear translocation, preserving NAD+/NADH ratio, suppressing intracellular ROS formation. These effects result from expressing antioxidant genes, maintaining mitochondrial function, reducing expression, preventing AIF translocation. mice, inhibited PAR-polymer formation, increased reduced TUNEL-positive retinal outer layer, ERGs, enhanced light chamber activity (all p values < 0.05). Our findings corroborate protects photoreceptors modulating SIRT1/PARP1 axis models degeneration.

Language: Английский

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Data Mining of Microarray Datasets in Translational Neuroscience

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(9), P. 1318 - 1318

Published: Sept. 14, 2023

Data mining involves the computational analysis of a plethora publicly available datasets to generate new hypotheses that can be further validated by experiments for improved understanding pathogenesis neurodegenerative diseases. Although number sequencing is on rise, microarray conducted diverse biological samples represent large collection with multiple web-based programs enable efficient and convenient data analysis. In this review, we first discuss selection associated neurological disorders, possibility combination datasets, from various types samples, conduct an integrated in order achieve holistic alterations examined system. We then summarize key approaches studies have made use obtain insights into translational neuroscience applications, including biomarker discovery, therapeutic development, elucidation pathogenic mechanisms gap bridged between improve utilization different together experimental validation, more comprehensive analyses. conclude providing future perspectives integrating multi-omics, advance precision phenotyping personalized medicine

Language: Английский

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Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 610 - 610

Published: Jan. 3, 2024

Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as 5 (Aqp5) knockdown provided enhanced sepsis survival in murine model. Potential AQP5 provide sulfonamides their derivatives. In this study, we tested hypothesis that reduce expression different conditions. The impact of on immune cell migration was examined lines REH RAW 264.7 qPCR, Western blot assay. Subsequently, whether furosemide methazolamide capable reducing after LPS incubation investigated whole blood samples healthy volunteers. Incubation with (10−5 M) (10−6 reduced mRNA protein about 30% cells. Pre-incubation cells towards SDF1-α compared non-preincubated control level. PBMCs led reduction LPS-induced levels, while failed it. Methazolamide appears However, administration, no longer possible. Hence, our study indicates has potential be used prophylaxis.

Language: Английский

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The Logistical Backbone of Photoreceptor Cell Function: Complementary Mechanisms of Dietary Vitamin A Receptors and Rhodopsin Transporters

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4278 - 4278

Published: April 12, 2024

In this review, we outline our current understanding of the mechanisms involved in absorption, storage, and transport dietary vitamin A to eye, trafficking rhodopsin protein photoreceptor outer segments, which encompasses logistical backbone required for cell function. Two key process are emphasized manuscript: ocular systemic membrane transporters, transporters. Understanding complementary responsible generation proper retinylidene segment will eventually shed light on importance genes encoded by these proteins, their relationship normal visual function pathophysiology retinal degenerative diseases.

Language: Английский

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Modifiers and their impact on inherited retinal diseases: a review

Ophthalmic Genetics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: Jan. 8, 2025

Background The phenotypic variability of inherited conditions can be due to several factors including environmental, epigenetic, and genetic. One those genetic is the presence modifying loci which alter expression a primary disease or phenotype-causing variant. Modifiers are known affect penetrance, dominance, expressivity, pleiotropy disease.

Language: Английский

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The Role of Gut Microbiota in Neuromyelitis Optica Spectrum Disorder

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3179 - 3179

Published: March 9, 2024

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling inflammatory disease of the central nervous system (CNS). Aquaporin-4 (AQP4)-specific T cells play key role in pathogenesis NMOSD. In addition to immune factors, recognizing AQP4 epitope showed cross-reactivity with homologous peptide sequences C. perfringens proteins, suggesting that gut microbiota plays an integral pathogenicity this review, we summarize research on involvement pathophysiology NMOSD and its possible pathogenic mechanisms. Among them, Clostridium Streptococcus have been confirmed by multiple studies. Based evidence, metabolites produced microbes, such as short-chain fatty acids (SCFAs), tryptophan (Trp), bile acid (BA) metabolites, also found affect cell metabolism. Therefore, very important. Alterations composition can lead pathological changes alter formation microbiota-derived components metabolites. It serve biomarker for onset progression potential disease-modifying therapy.

Language: Английский

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Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs)

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1117 - 1117

Published: May 5, 2025

Background: Next Generation Sequencing (NGS) Technology has represented a revolution in the molecular characterization of Inherited Retinal Dystrophies (IRDs), which are among most genetically and phenotypically heterogeneous conditions. NGS allowed consistent number patients affected by IRDs, but at same time, unexpected results can pose diagnostic dilemmas. Aim: The purpose this review is to describe possible scenarios as reference for ophthalmologists geneticists who involved particularly complex field. Methods: A existing literature been performed. In addition, examples have brought, from series that analyzed University Naples “Federico II”-CEINGE Biotecnologie Avanzate “Franco Salvatore”. Results: Unexpected genetic IRDs not uncommon. main findings additional variants potentially modify phenotypes, deletions masked apparent homozygosity, pathogenic leading phenotypes revisitation. Conclusions: high phenotypic heterogeneity characterizing greatly advantaged advent Technology. At uncommon finding data poses criticisms need be addressed. review, we scenarios, go through some more genotype–phenotype correlations.

Language: Английский

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The molecular genetics of anterior segment dysgenesis

Experimental Eye Research, Journal Year: 2023, Volume and Issue: 234, P. 109603 - 109603

Published: July 24, 2023

Language: Английский

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