Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Injectable anti-inflammatory supramolecular nanofiber hydrogel to promote ranibizumab therapy in age-related macular degeneration treatment

ABSTRACT: The exact pathogenesis of age-related macular degeneration (AMD) leading to visual impairment and severe vision loss is still unclear, and the currently available treatments are often unsatisfactory. Previous studies have demonstrated both oxidative stress-induced damage to the retinal pigment epithelium (RPE) and inflammation are involved in AMD. Although anti-vascular endothelial growth factor (VEGF) therapy can impair the growth of new blood vessels, serious side effects were found with repeated monthly intravitreal injections. Here, an injectable hydrogel based on an anti-inflammatory betamethasone phosphate (BetP) drug (BetP-Gel) was designed to enable long-term efficient release of ranibizumab (RZB) to attenuate choroidal neovascularization (CNV), reduce vascular leakage and inhibit vascular proliferation in the retina, which significantly increased the effective treatment time of ranibizumab compared with that in clinical practice. In particular, experimental data with in vitro and in vivo models revealed that BetP-Gel itself had a strong ability to scavenge intracellular reactive oxygen species (ROS) and reduce tumour necrosis factor-α (TNF-α) as well as interleukin (IL-1β, IL-6, IL-8, and IL-18) inflammatory cytokines, inhibiting ROS- and inflammation-induced retinal damage. Altogether, the carrier-free system (RZB@BetP-Gel) could serve as a novel antioxidant, anti-inflammatory and anti-neovascularization agent for the treatment of AMD.

ORGANISM(S): Mus musculus

PROVIDER: GSE165702 | GEO | 2024/01/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Single-cell transcriptome of wet AMD patient-derived endothelial cells in angiogenic sprouting

Project description:Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome (https://christinecheunglab.shinyapps.io/human_wet_AMD_sprouting/) has been created to facilitate further discovery research.

2022-11-02 | GSE213933 | GEO

IL-4 protects against chemically-induced retinal degeneration in AMD mouse model via Nrf2 activation

Project description:To explore whether IL-4 could exert a novel protective role for RPE damage and attenuate the pathogenesis of dry age-related macular degeneration (AMD), we established a retinal degeneration model of dry AMD by intravenous injection of NaIO3, and explored the treatment effects of intravitreal IL-4 injection. We found exogenous IL-4 protected against retinal degeneration characterized by well-preserved structures and improved retinal function. The RNA-seq analysis revealed that IL-4 treatment suppressed the essential oxidative and pro-inflammatory pathways in the degenerative retina. IL-4 induced the expression of IL-4Rα and Nrf2 for anti-oxidative defense in vivo and in vitro. Our data provides evidences that IL-4 can be a useful neuroprotective agent against retinal degeneration due to its antioxidant and anti-inflammatory property through Nrf2 activation. The IL-4/IL-4Rα-Nrf2 axis maybe the potential targets for the development of novel therapies for dry AMD.

2022-12-17 | GSE193808 | GEO

RNA analysis of the circadian rhythm of choroidal neovascularization

Project description:Many diseases that affect the heart, brain, and even the eyes originate from vascular pathology, emphasizing the role of vascular regulation. In age-related macular degeneration (AMD), excessive growth of abnormal blood vessels in the eye (choroidal neovascularization) ultimately leads to detachment of retinal pigment epithelium and decreased vision, indicating the importance of choroidal neovascularization in the treatment of age-related diseases. The circadian clock in the mammalian retina regulates various retinal functions, enabling the retina to adapt to the light dark cycle. Emerging evidence suggests a link between circadian clock and retinopathy, but the causal relationship has not yet been determined.

2024-10-09 | GSE253949 | GEO

COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

Project description:Neovascularization contributes to multiple visual disorders including age-related macular degeneration (AMD). Current therapies for treating ocular angiogenesis are centered on the inhibition of vascular endothelial growth factor (VEGF). While clinically effective, some AMD patients are refractory or develop resistance to anti-VEGF and concerns of increased risks of developing geographic atrophy following long-term treatment have been raised. Identification of alternative pathways to inhibit pathological angiogenesis is thus important. We have identified a novel inhibitor of angiogenesis, COCO/DAND5, a member of the Cerberus-related DAN family. We demonstrate that COCO inhibits sprouting, migration and cellular proliferation of cultured endothelial cells. Intravitreal injections of COCO inhibited retinal vascularization during development and in models of retinopathy of prematurity and AMD. COCO equally abrogated angiogenesis in choroid explants and in a model of choroidal neovascularization. Mechanistically, COCO inhibited the expression of TGFβ and BMP pathwaysand altered ATP production, glucose uptake and redox balance of endothelial cells. Together, these data show that COCO is an inhibitor of retinal and choroidal angiogenesis, possibly representing a therapeutic option for the treatment of neovascular ocular diseases.

2020-12-22 | GSE160099 | GEO

Research on Downstream Binding Proteins of PlexinB1 in Human Brain Vascular Pericytes

Project description:Age-related macular degeneration (AMD) is a prevalent neuroinflammation condition and the leading cause of irreversible blindness among the elderly population. Smoking significantly increases AMD risk, yet the mechanisms remain unclear. Here, we investigated the role of Sema4D-PlexinB1 axis in the progression of AMD, in which Sema4D-PlexinB1 is highly activated by smoking. Using patient-derived samples and mouse models, we discovered that smoking increased the presence of Sema4D on the surface of CD8+ T cells that migrated into the choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 axis and interacted with its receptor PlexinB1 on choroidal pericytes. This led to ROR2-mediated PlexinB1 phosphorylation and pericytes activation, hence disrupted vascular homeostasis and promoted neovascularization. Inhibition of Sema4D reduced CNV and improved the benefit of anti-VEGF treatment. In conclusion, this study unveils the molecular mechanisms through which smoking exacerbates AMD pathology, and presents a potential therapeutic strategy by targeting Sema4D to augment current AMD treatments.

2025-01-26 | PXD059165 | Pride

Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes [scRNA-seq]

2025-01-26 | GSE288036 | GEO

Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes [bulk RNA-seq]

2025-01-26 | GSE288035 | GEO

Intermittent fasting alleviates photoreceptor degeneration and retina inflammation in oxidative stress-induced model of Age-Related Macular Degeneration

Project description:Age-related macular degeneration (AMD), a prevalent neurodegenerative disorder, remains the leading cause of vision loss among the elderly population. Despite the urgent need, effective treatments or preventive strategies for AMD are not available. Recent studies have highlighted the potential neuroprotective benefits of intermittent fasting (IF) in several models of aging and age-associated disorders. However, its efficacy in AMD has not been established. Our current research reveals that IF alleviated neurodegeneration by reducing RPE and photoreceptor cell damage in an oxidative stress-induced mouse model of AMD. The assessment of visual capabilities in mice through optomotor response (OMR) tests indicates that IF markedly preserved visual function in NaIO3-treated mice. To understand the mechanism by which IF exerts its protective effects, we performed transcriptome analyses and found that IF can counteract numerous transcriptional alterations induced by NaIO3, predominantly affecting genes involved in photoreceptor structure, inflammatory pathways and reactive oxygen species (ROS) process. Further, we demonstrated through multiple experiments that IF could effectively reduce ROS levels and restraining the hyperactivation of microglia and Müller cells within the RPE and retina. Moreover, we explored the initiation of IF at a later stage in an individual's lifespan and found that benefits were also obtained in the AMD model. Collectively, this study indicates IF exerts neuroprotective effects by reducing ROS production and inflammation in the retina, and is expected to become a new strategy for retinal degenerative diseases caused by oxidative damage, incluiding AMD.

2024-07-09 | GSE271791 | GEO

Feedback regulation between ALKBH3-mediated glycolysis and histone lactylation promotes age-related macular degeneration

Project description:Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Using clinical samples and knockout mice, we reported that the m1A eraser ALKBH3 reshaped retinal metabolism to promote AMD. In retinal pigment epithelium (RPE), the dm1ACRISPR system demonstrated that ALKBH3 demethylated the glycolytic enzyme HK2 to activate anaerobic glycolysis, producing excessive lactate. The lactate promoted histone lactylation at H3K18, which in turn bound to ALKBH3 to amplify its transcription, establishing a positive feedback loop. The ALKBH3 inhibitor HUHS015 disrupted this loop, effectively mitigating RPE degeneration. Furthermore, ALKBH3 directly targeted the pro-angiogenic factor VEGFA to modulate the metabolic cross-talk between RPE and choroidal capillaries, thus promoting choroidal neovascularization (CNV). HUHS015 inhibited CNV synergistically with the anti-VEGF drug Aflibercept. Our study provides critical insights into the molecular mechanisms and metabolic events facilitating the progression from RPE degeneration to CNV in AMD, laying the groundwork for new treatments of AMD.

2024-08-14 | GSE274399 | GEO

Comparative analysis of Retinal Angiogenesis during Inflammatory stage

Project description:Choroidal neovascularization (CNV) and the resulting retinal angiogenesis are pathological hallmarks of wet Age-related macular degeneration (AMD). The pathogenesis of CNV is not fully understood, but accumulated evidence has suggested the role of inflammation in the early stage of CNV. To better understand the molecular landscape during the early stage, we performed RNA-Seq and mass spectrometry-based proteomic analysis in the retina of the laser-induced CNV mouse model. Both transcriptomic and proteomic data showed dramatic activation of inflammatory response 3 days post photocoagulation. Integrative analysis suggested a moderate correlation between RNA-Seq and mass spec. Up-regulation of angiogenic factor, basic fibroblast growth factor-2 (Fgf-2), but not vascular endothelial growth factor (Vegf) was observed at both RNA and protein levels, highlighting Fgf-2 as a biomarker and potential therapeutic target during the early stage of CNV. In addition, enrichment analysis indicated a large overlap of inflammation-related genes and pathways at both levels. We also compared our findings with human retinal RNA-Seq data from AMD patients and controls. By using a multi-omics and comparative approach, our findings demonstrate the molecular landscape during the inflammatory stage of mouse CNV and provided new insight into the translation from the mouse model to understanding human AMD and its potential intervention and therapies.

2024-01-17 | GSE207171 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data