Single-cell Transcriptomics Unravel Stereocilia Degeneration as a Key Contributor to Age-related Vestibular Dysfunction in Mice and Humans

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Abstract Age-related vestibular dysfunction (ARVD) is a prevalent, debilitating condition in the elderly. The etiology and molecular mechanisms are poorly understood. We focused on mechanosensitive hair cells (HCs) as they particularly vulnerable to aging. Using single-cell RNA-seq transcriptomes of young old mouse HCs, we show that aging HCs display both universal blueprints, such genomic instability, mitochondrial dysfunction, impaired proteostasis, cell type-specific signatures associated with deterioration bundles mechanotransduction. These also observed aged human suggesting shared mechanisms. Importantly, morphological functional analysis revealed bundle degeneration decline precede HC loss, highlighting mechanotransduction key contributor ARVD. Furthermore, cellular changes less pronounced than cochlear underscoring different pace between two mammalian inner ear sensory epithelia.

Язык: Английский

---

Crosstalk between signaling pathways (Rho/ROCK, TGF-β and Wnt/β-Catenin Pathways/ PI3K-AKT-mTOR) in Cataract: A Mechanistic Exploration and therapeutic strategy

Gene, Год журнала: 2025, Номер unknown, С. 149338 - 149338

Опубликована: Фев. 1, 2025

Язык: Английский

---

Exposure Assessments of Cadmium and Lead with Age-Related Eye Disease: A Systematic Review and Meta-Analysis

Journal of Trace Elements in Medicine and Biology, Год журнала: 2025, Номер 89, С. 127631 - 127631

Опубликована: Март 16, 2025

Язык: Английский

---

Nucleolar ribosomal RNA synthesis continues in differentiating lens fiber cells until abrupt nuclear degradation required for ocular lens transparency

RNA Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Cellular differentiation requires highly coordinated action of all three transcriptional systems to produce rRNAs, mRNAs, and various 'short' 'long' non-coding RNAs by RNA Polymerase I, II, III systems, respectively. The I catalyzes transcription about 400 copies mammalian rDNA genes, generating 18S, 5.8S, 28S rRNA molecules. Lens fibre cell is a unique process study mechanisms individual crystallin genes as their very high outputs are directly comparable only globin in erythrocytes. Importantly, both terminally differentiated lens cells erythrocytes degrade nuclei though different mechanisms. In lens, the generation organelle-free zone (OFZ) includes degradation mitochondria, endoplasmic reticulum, Golgi apparatus, nuclei. Here, using fluorescence situ hybridization (FISH) we evaluated nascent transcription, located nucleoli, during mouse differentiation. undergo morphological changes including chromatin condensation prior denucleation. Remarkably, persists that direct proximity OFZ. Additionally, nucleoli shape were via immunofluorescence detection fibrillarin, nucleolin, UBF, other proteins. These studies demonstrate for first time condensed have capacity support transcription. Thus, propose 'late' production molecules consequently ribosomes increases protein synthesis machinery within mature fibres.

Язык: Английский

---

Exploring causal relationships between circulating micronutrients and age-related eye diseases: a Mendelian randomization study

Genes & Nutrition, Год журнала: 2025, Номер 20(1)

Опубликована: Март 28, 2025

With the global population aging, age-related eye diseases (AREDs) such as senile cataract (SC), macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are becoming increasingly significant public health concerns. The rising prevalence of AREDs underscores urgent need for effective prevention treatment strategies. This study aimed to explore causal relationships between circulating micronutrients (CMs) AREDs. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted using genetic variants instrumental variables assess effects fifteen CMs (vitamin A, vitamin B6, B12, C, D, E, folate, carotene, copper, calcium, iron, magnesium, potassium, selenium, zinc) on Data were sourced from large-scale genome-wide association studies (GWAS). primary analytical method employed inverse-variance weighted (IVW), supplemented by sensitivity analyses confirm robustness results. MR revealed protective selenium against SC (OR = 0.961, 95% CI 0.932–0.991, P 0.012) DR 0.927, 0.870–0.987, 0.019). Furthermore, higher genetically predicted magnesium levels associated with a reduced risk AMD 0.679, 0.515–0.895, 0.006). However, no observed other glaucoma or These findings provided valuable insights into complex interplay AREDs, offering potential pathways developing targeted nutritional interventions strategies mitigate these debilitating conditions.

Язык: Английский

---

Enhancing Ocular Health Precision: Cataract Detection Using Fundus Images and ResNet-50

IECE transactions on intelligent systematics., Год журнала: 2024, Номер 1(3), С. 145 - 160

Опубликована: Окт. 29, 2024

Cataracts are a leading cause of blindness in Pakistan, contributing to more than 54% cases due poor living condition, nutritional deficiencies, and limited healthcare access. Early detection is critical avoid invasive treatments,but current diagnostic approaches often identify cataracts at advanced stages. This paper presents an advanced,automated cataract system using deep learning specifically the ResNet-50 architecture, address this gap. The model processes fundus retinal images curated from diverse datasets, classified by ophthalmologic experts through rigorous three-stage process. By leveraging model, categorized into normal,moderate,and severe, achieving accuracy 97.56% on full images. Notably, performs well even partial with 70% visibility, maintaining 95.23%, thus minimizing need for extensive restoration. dataset was augmented include 17,500 images,ensuring robust training. model's ability detect high precision varying visibility(70% ,80%,85% beyond) demonstrate its flexibility reliability, consistently above 95.50%. research offers non-invasive, efficient solution particularly suited remote areas, addressing limitations late-stage diagnoses. It represent significant advancement has potential revolutionize global identification early, accurate intervention.

Язык: Английский

---

The reduction of LEDD leads to visual dysfunction in patients with PD after STN-DBS: a randomized clinical trial

International Journal of Surgery, Год журнала: 2024, Номер 111(1), С. 650 - 660

Опубликована: Авг. 5, 2024

Medication adjustment after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) may influence visual function. However, no clinical trials have been designed specifically to investigate this effect. To compare effects levodopa-equivalent daily dose (LEDD) reduction and non-reduction on function following STN-DBS. This was a multi-center, prospective, randomized, double-blinded trial. A total 208 were referred for DBS between June 2019 July 2021 analyzed 2023 2023. STN-DBS performed, LEDD reduced one study arm but not other. The primary outcome measure impairment questionnaire (VIPD-Q) or without 12 months postoperatively, secondary outcomes included retinal nerve fiber layer (RNFL) thickness, vessel density, eye-tracking system results, contrast sensitivity field. During short-term follow-up, implantation did significantly affect (VIPD-Q, baseline vs. 1 month, 9.269±8.385 8.938±7.666, Mann-Whitney U tests; P=0.6746). In long-term group demonstrated significant decline function, RNFL density compared control (P<0.001). Visual dysfunction, particularly thinner lower is related Prolonged administration dopamine-mimetic drugs prevents symptoms. Thus, physicians should consider when report dysfunction before surgery severe symptoms

Язык: Английский

---

Change in visual acuity over a 12-year period predicts cognitive decline in older adults: identifying social engagement as a potential mediator

Aging & Mental Health, Год журнала: 2024, Номер unknown, С. 1 - 7

Опубликована: Ноя. 20, 2024

Deterioration in vision is an important dementia risk factor yet few studies have examined objectively measured changes visual acuity over time. Visual decline may also reduce social engagement, highlighting the need to examine concert with broader function.

Язык: Английский

---

In the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12817 - 12817

Опубликована: Ноя. 28, 2024

Water exists in the beginning and hydrates all matter. Life emerged water, requiring three essential components compartmentalized spaces: (1) universal energy sources driving biochemical reactions processes, (2) molecules that store, encode, transmit information, (3) functional players carrying out biological activities structural organization. Phosphorus has been selected to create adenosine triphosphate (ATP) as currency, nucleic acids for genetic information storage transmission, phospholipids cellular compartmentalization. Meanwhile, proteins composed of 20 α-amino have evolved into extremely diverse three-dimensional forms, including folded domains, intrinsically disordered regions (IDRs), membrane-bound fulfill roles. This review examines several unique findings: insoluble proteins, membrane can become solubilized unsalted while cytosolic acquire membrane-inserting capacity; Hofmeister salts affect protein stability by targeting hydration; ATP biphasically modulates liquid-liquid phase separation (LLPS) IDRs; (4) antagonizes crowding-induced destabilization; (5) triphosphates highest efficiency inducing folding. These findings imply following: hydration might be encoded sequences, central manifestation modulation structures, dynamics, functionalities; phosphate anions a capacity enhancing μs-ms likely through ionic state exchanges shell, underpinning ATP, polyphosphate, molecular chaperones folding; linking with adenosine, acquired spacetime-specifically release modulate hydration, thus possessing myriad energy-dependent -independent functions. In light success AlphaFolds accurately predicting structures neural networks store distributed patterns across nodes, fundamental question arises: Could also handle similarly but more intricate coding, topological architectures, spacetime-specific supply membrane-compartmentalized aqueous environments?

Язык: Английский

---

FADS1 inhibition protects retinal pigment epithelium cells from ferroptosis in age related macular degeneration

European Journal of Pharmacology, Год журнала: 2024, Номер unknown, С. 177227 - 177227

Опубликована: Дек. 1, 2024

Язык: Английский

---