Altered Elastin Turnover, Immune Response, and Age-Related Retinal Thinning in a Transgenic Mouse Model With RPE-Specific HTRA1 Overexpression DOI Creative Commons

Soumya Navneet,

Masaaki Ishii,

Bärbel Rohrer

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(8), P. 34 - 34

Published: July 19, 2024

Purpose: A single-nucleotide polymorphism in HTRA1 has been linked to age-related macular degeneration (AMD). Here we investigated the potential links between retinal changes, elastin turnover, autoantibody production, and complement C3 deposition a mouse model with RPE-specific human overexpression. Methods: transgenic mice age-matched CD1 wild-type were analyzed at 6 weeks 4, 6, 12 14 months of age using vivo imaging by optical coherence tomography (OCT) fundus photography, as well molecular readouts, focusing on elastin-derived peptide quantification, antielastin autoantibody, total Ig antibody measurements immunohistochemistry examine elastin, IgG, protein levels sections. Results: OCT indicated thinning inner nuclear layer an early phenotype mice, followed age/genotype-related photoreceptor layer, RPE, retina. exhibited reduced RPE/choroid increased breakdown products retina serum. corresponding age-dependent increase serum IgG IgM autoantibodies was observed. In RPE/choroid, these changes associated deposition. Conclusions: Our results confirm that overexpression induces certain AMD-like phenotypes mice. This includes altered immune response, addition outer thinning. The identification peptides autoantibodies, together provides rationale for overactive system AMD irrespective underlying genetic risk.

Language: Английский

Co-delivery of antioxidants and siRNA-VEGF: promising treatment for age-related macular degeneration DOI
Marina França Dias, Estael Luzia Coelho da Cruz-Cazarim, Frederico Pittella

et al.

Drug Delivery and Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

1
Dicer loss in Muller glia leads to a defined sequence of pathological events beginning with cone dysfunction DOI Open Access

Daniel Larbi,

Alexander M. Rief,

Seoyoung Kang

et al.

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

Published: Feb. 1, 2025

Abstract Purpose The loss of Dicer in Müller glia (MG) results severe photoreceptor degeneration as it occurs retinitis pigmentosa or AMD. However, the sequence events leading to this degenerative state is unknown. aim study was conduct a chronological functional and structural characterization pathological MG-specific Dicer-cKO mice vivo histologically. Methods To delete mature microRNAs (miRNAs) MG, two conditional Dicer1 knock-out mouse strains namely RlbpCre:Dicer-cKO MG GlastCre:Dicer-cKO were created. Optical coherence tomography (OCT), electroretinograms (ERGs) well histological analyses conducted investigate changes up six months after deletion. Results Dicer/miRNA leads 1) impairments external limiting membrane (ELM) – retinal pigment epithelium (RPE), 2) cone dysfunction 3) remodeling inner retina, 1, 3 6 loss, respectively, both strains. Furthermore, Rlbp:Dicer-cKO strain, rod impairment found 4 depletion (4) accompanied by alteration RPE integrity (5). Conclusions adult retina impacts function prior any measurable function, suggesting pivotal role for miRNAs supporting health. A partially impaired however seems accelerate overall events.

Language: Английский

Citations

0
Hydrophobic vehicles for hydrophilic drugs: Sustained intravitreal caffeine delivery with oleogels DOI
Nan Jiang, Wei Guo, Siyu Wang

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 490 - 502

Published: Feb. 11, 2025

Language: Английский

Citations

0
MSC Exosomes and MSC Exosomes Loaded with LncRNA H19 as Nanotherapeutics Regulate the Neurogenetic Potential of Müller Glial Cells in Dry Age-Related Macular Degeneration DOI
Yue Tang,

Caiyi Cheng,

Rui Ding

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Dicer Loss in Müller Glia Leads to a Defined Sequence of Pathological Events Beginning With Cone Dysfunction DOI Creative Commons

Daniel Larbi,

Alexander M. Rief,

Seoyoung Kang

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(3), P. 7 - 7

Published: March 4, 2025

The loss of Dicer in Müller glia (MG) results severe photoreceptor degeneration, as it occurs retinitis pigmentosa or age-related macular degeneration; however, the sequence events leading to this degenerative state is unknown. aim study was conduct a chronological functional and structural characterization pathological MG-specific Dicer-conditional knockout (cKO) mice vivo histologically. To delete mature microRNAs (miRNAs) MG, two conditional Dicer1 mouse strains (Rlbp-CreER:tdTomato:Dicer-cKOMG Glast-CreER:tdTomato:Dicer-cKOMG) were created. Optical coherence tomography (OCT), electroretinograms (ERGs), histological analyses conducted investigate changes up 6 months after deletion. Dicer/miRNA MG leads (1) impairments area spanning from external limiting membrane (ELM) retinal pigment epithelium (RPE), (2) cone dysfunction, (3) remodeling inner retina at 1, 3, loss, respectively, both strains. Furthermore, Rlbp-CreER:tdTomato:Dicer-cKOMG strain, rod impairment found 4 depletion (4) accompanied by alteration RPE integrity (5). adult impacts function prior any measurable function, suggesting pivotal role for miRNAs supporting health. A partially impaired RPE, seems accelerate degeneration overall events.

Language: Английский

Citations

0
Obesity‐related early structural alterations in the retina detected by optical coherence tomography DOI Creative Commons

Maide Gözde İnam,

Onur İnam,

Doru Gucer

et al.

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

This retrospective cross-sectional study, using retinal spectral-domain optical coherence tomography (SD-OCT) scans, investigated obesity-related structural alterations in the retina. Ninety-two eyes of 92 healthy asymptomatic participants were categorized into two groups based on body mass index (BMI) measurements: non-obese (BMI < 25, 45%) and pre-obese/obese ≥ 55%) to compare imaging parameters different layers. Structural parameters, including thickness volume values, obtained across distinct layers segmented SD-OCT scans. The nerve fibre layer was lower high-BMI group than low-BMI (p = 0.048). However, presented significantly higher inner nuclear 0.036). In region analysis, difference prominent superior 0.033) inferior 0.001) parafoveal nasal perifoveal 0.041) regions, while changes 0.009) regions. A stepwise hierarchical binary logistic regression model, controlling for age gender, pointed significant associations regionally decreased increased with high BMI 0.001). Retinal detected between healthy, individuals groups. Besides a layer, increase BMI, possibly due Müller glia responses osmotic, metabolic inflammatory stress, awaiting further investigation.

Language: Английский

Citations

0
Physiology and pathophysiology of the retinal neuroglia DOI
Antje Grosche,

Jens Grosche,

Alexei Verkhratsky

et al.

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 239 - 265

Published: Jan. 1, 2025

Language: Английский

Citations

0
The complement pathway as a therapeutic target for neovascular age-related macular degeneration-mediated subretinal fibrosis DOI Creative Commons
Heping Xu,

Caijiao Yi,

Mei Chen

et al.

Current Opinion in Pharmacology, Journal Year: 2024, Volume and Issue: 76, P. 102448 - 102448

Published: March 30, 2024

Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in elderly developed countries. Intravitreal injection VEGF inhibitors mainstream therapy for nAMD, although nearly 50% patients do not respond or poorly to therapy. One main reasons poor outcome development subretinal fibrosis, a process excessive deposition extracellular matrix proteins around diseased blood vessels. Currently, there no medication prevent treat condition. Here, we discussed recent advances pathogenesis nAMD-mediated with focus on role complement system. We further proposed approaches target system management fibrosis and highlighted area research future clinical applications complement-based

Language: Английский

Citations

2
HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy DOI Creative Commons

Uma Maheswari Deshetty,

Nivedita Chatterjee, Shilpa Buch

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 903 - 903

Published: June 3, 2024

Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced occurrence comorbidities, including ocular manifestations. The involvement endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation cellular senescence or role initiating senescent traits. This study investigated how ER dysregulated autophagy impact triggered by Tat MIO-M1 cell line (human Müller glial cells). Cells exposed to exhibited increased vimentin expression combined markers (BiP, p-eIF2α), (LC3, Beclin-1, p62), marker p21 compared control cells. Western blotting staining techniques like SA-β-gal were employed examine these markers. Additionally, inhibitor 4-PBA before exposure led a decreased stress, senescence, Conversely, pre-treatment 3-MA resulted but did not alter findings suggest link between autophagy, initiation phenotype cells induced exposure.

Language: Английский

Citations

1
Retinal Inflammation and Reactive Müller Cells: Neurotrophins’ Release and Neuroprotective Strategies DOI Creative Commons
Bijorn Omar Balzamino, Andrea Cacciamani, Lucia Dinice

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(12), P. 1030 - 1030

Published: Dec. 9, 2024

Millions of people worldwide suffer from retinal disorders. Retinal diseases require prompt attention to restore function or reduce progressive impairments. Genetics, epigenetics, life-styling/quality and external environmental factors may contribute developing diseases. In the physiological retina, some glial cell types sustain neuron activities by guaranteeing ion homeostasis allowing effective interaction in synaptic transmission. Upon insults, cells interact with neuronal other non-neuronal cells, at least part counteracting biomolecular changes that trigger complications vision loss. Several epigenetic oxidative stress mechanisms are quickly activated release concert growth, fibrogenic angiogenic can influence overall microenvironment cell-to-cell response. Reactive Müller participate secreting neurotrophic/growth/angiogenic factors, cytokines/chemokines, cytotoxic/stress molecules neurogenic inflammation peptides. Any attempt maintain/restore condition be interrupted perpetuating vascular dysfunction neurodegeneration. Herein, we critically revise current knowledge on cell-to-mediator interplay between astrocytes microglia, respect pro-con modulators neuroprotective/detrimental activities, as observed using experimental models analyzing ocular fluids, altogether contributing a new point view field research precision medicine.

Language: Английский

Citations

1