An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice DOI Creative Commons
Lorena Olivares‐González, Sheyla Velasco, Idoia Gallego

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 12(1), P. 98 - 98

Published: Dec. 30, 2022

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on degeneration activation in rd10 mice, a model RP, as well LPS-stimulated BV2 cells. The EFA was orally administered to mice from postnatal day (P)9 P18. At P18, electrical activity retina examined electroretinography (ERG) innate behavior response light were measured. Retinal studied via histology TUNEL assay immunolabeling. Microglia polarization (M1/M2) assessed flow cytometry, qPCR, ELISA histology. Redox status analyzed measuring antioxidant enzymes markers oxidative damage. Interestingly, ameliorated dysfunction improving ERG recording sensitivity light, reducing photoreceptor cell reduced inflammation attenuating inducing shift M2 phenotype mouse retinas also stress lipid peroxidation carbonylation. These findings could open up new therapeutic opportunities based resolving with oral supplementation SPMs such supplement.

Language: Английский

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases DOI Creative Commons
Rosalía Fernández‐Calle, Sabine C. Konings, Javier Frontiñán-Rubio

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Sept. 24, 2022

Abstract ApoE is the major lipid and cholesterol carrier in CNS. There are three human polymorphisms, apoE2, apoE3, apoE4, genetic expression of APOE4 one most influential risk factors for development late-onset Alzheimer's disease (AD). Neuroinflammation has become third hallmark AD, together with Amyloid-β plaques neurofibrillary tangles hyperphosphorylated aggregated tau protein. This review aims to broadly extensively describe differential aspects concerning apoE. Starting from evolution apoE how APOE's single-nucleotide polymorphisms affect its structure, function, involvement during health disease. reflects on impact critical AD pathology, such as neuroinflammatory response, particularly effect APOE astrocytic microglial function dynamics, synaptic amyloid-β load, autophagy, cell–cell communication. We discuss affecting pathology combined genotype, sex, age, diet, physical exercise, current therapies clinical trials field. The genotype other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, multiple also addressed. Therefore, this gathers relevant findings related up date implications CNS pathologies provide a deeper understanding knowledge

Language: Английский

Citations

154

Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma DOI
Yanying Miao, Guoli Zhao, Shuo Cheng

et al.

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 93, P. 101169 - 101169

Published: Feb. 1, 2023

Language: Английский

Citations

49

Latent epigenetic programs in Müller glia contribute to stress and disease response in the retina DOI
Jacqueline L. Norrie,

Marybeth Lupo,

Danielle R. Little

et al.

Developmental Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

4

The mechanism and therapeutic strategies for neovascular glaucoma secondary to diabetic retinopathy DOI Creative Commons
Yizhen Tang, Yan Shi, Zhigang Fan

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 23, 2023

Neovascular glaucoma (NVG) is a devastating secondary characterized by the appearance of neovascular over iris and proliferation fibrovascular tissue in anterior chamber angle. Proliferative diabetic retinopathy (PDR) one leading causes NVG. Currently increasing diabetes population drive prevalence rate NVG into fast-rising lane. The pathogenesis underlying makes it refractory to routine management for other types clinical practice. combination panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (VEGF) injections, anti-glaucoma drugs, surgical intervention as well blood glucose control needed. Early diagnosis aggressive treatment time are crucial halting neovascularization process preserving vision. This review provides an overview (DR), including epidemiology, management, so provide better understanding potential therapeutic strategies future treatment.

Language: Английский

Citations

33

Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation DOI Open Access
Xudong Wang, Tianxi Wang,

Enton Lam

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12090 - 12090

Published: July 28, 2023

The eye is an immune privileged tissue that insulates the visual system from local and systemic provocation to preserve homeostatic functions of highly specialized retinal neural cells. If privilege breached, stimuli will invade subsequently trigger acute inflammatory responses. Local resident microglia become active release numerous immunological factors protect integrity Although responses are necessary control eradicate insults eye, chronic inflammation can cause damage cell dysfunction, leading ocular disease vision loss. In this review, we summarized features in retina key responses, factors, intracellular pathways activated when fails, as well a highlight recent clinical research advances immunity vascular diseases including retinopathy prematurity, age-related macular degeneration, diabetic retinopathy.

Language: Английский

Citations

26

Inhibiting HMGB1/AGER/NF-κB pathway prevents pro-inflammatory microglia polarization and protect photoreceptors in retinitis pigmentosa DOI Creative Commons

Chaojun Hu,

Tao Cui, Zihang Xu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114192 - 114192

Published: Feb. 3, 2025

Retinitis pigmentosa (RP) is an inherited retinal neurodegenerative disease which a significant contributor to blindness. Microglia-mediated inflammation plays crucial role in retinitis pigmentosa. However, the activation mechanisms of microglia and polarized RP remain unclear. High-mobility group box 1 (HMGB1) key aseptic inflammation, glycyrrhizin exerts anti-inflammatory effects by targeting HMGB1. This study aimed investigate HMGB1 explore protective on photoreceptors. Male C57BL/6 mice age-matched rd1 were used for vivo models, while zaprinast-treated 661w cells HMGB1-treated BV-2 vitro models. In this study, expression was analyzed using QPCR western blot (WB). Immunofluorescence staining ELISA performed assess translocation secretion. Glycyrrhizin inhibit HMGB1, FPS-ZM1 served as inhibitor receptor advanced glycation end products (AGER). Microglial polarization evaluated QPCR, HMGB1/ AGER/ NF-κB signaling pathway through WB. Photoreceptor degeneration visual function assessed H&E staining, electroretinography, TUNEL staining. We observed elevated levels retina demonstrated that photoreceptors may serve source retina. Additionally, cause microglial via HMGB1/AGER/ secrete inflammatory factors including TNF-α IL-1β accelerates reversed loss pathway. Our findings showed secreted activated HMGB1/AGER/NF-κB caused delayed progression vivo, presenting potential novel approach treating

Language: Английский

Citations

1

Models of microglia depletion and replenishment elicit protective effects to alleviate vascular and neuronal damage in the diabetic murine retina DOI Creative Commons
Kaira A. Church, Derek Rodriguez,

Difernando Vanegas

et al.

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Dec. 14, 2022

Abstract Microglia, the resident phagocytes of retina, are believed to influence development retinopathy, but their exact contributions vascular integrity and neuronal loss unknown. Therefore, utilizing two models microglia depletion, we aimed deplete repopulate clarify contribution damage in diabetic retina an STZ-induced model hyperglycemia. Here, report that 2 weeks exposure diphtheria toxin (DTx) CX3CR1 CreER :R26 iDTR transgenic mice induced a 62% increase Iba1 + associated with TUJ1 axonal density prevention NeuN RBPMS loss. Conversely, PBS controls exhibited robust compared non-diabetic controls. A 2-week recovery period from DTx was 40% reduction angiogenesis 85% fibrinogen deposition into comparison PBS-treated Analysis morphology marker expression revealed following displayed P2RY12 Ly6C – phenotype high transformation index (TI) values complimented by ramified-surveillant closely resembling In contrast, control microglia, 50% TI amoeboid morphology. To validate these observations were due used PLX-5622 assess retinas mice. Confocal microscopy also prevented extravasation retina. mRNAseq gene analysis retinal isolates PLX-5622-induced depletion repopulation downregulation genes microglial activation phagocytosis, B2m , Cx3cr1, Trem2 complement-associated synaptic pruning, C1qa C1qb C1qc . Although levels those CSF-1R antagonists distinct, our results suggest replenishment is neuroprotective inducing proliferation homeostatic pool supports integrity.

Language: Английский

Citations

29

Selective drug delivery to the retinal cells: Biological barriers and avenues DOI Creative Commons
Eva Ramsay, Tatu Lajunen, Madhushree Bhattacharya

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 361, P. 1 - 19

Published: July 27, 2023

Retinal drug delivery is a challenging, but important task, because most retinal diseases are still without any proper therapy. Drug to the retina hampered by anatomical and physiological barriers resulting in minimal bioavailability after topical ocular systemic administrations. Intravitreal injections current method-of-choice delivery, these show short duration of action for small molecules low target many protein, gene based drugs nanomedicines. State-of-art systems on prolonged retention, controlled release physical features (e.g. size charge). However, not cell-specific approaches do facilitate intracellular modern biological proteins, RNA medicines, editing). In this focused review we highlight factors mechanisms that form basis selective future. Therefore, presenting knowledge related membrane transporters, receptors targeting ligands relation nanomedicines, conjugates, extracellular vesicles, melanin binding. These issues discussed light structure cell types as well future prospects field. Unlike some other fields targeted cancer research), technologies have been rarely studied, even though may be more feasible local administration into eye.

Language: Английский

Citations

22

Engineered Extracellular Vesicles for Delivery of an IL‐1 Receptor Antagonist Promote Targeted Repair of Retinal Degeneration DOI

Yizong Liu,

Peng Xia,

Feiyue Yan

et al.

Small, Journal Year: 2023, Volume and Issue: 19(46)

Published: July 30, 2023

Abstract Retinal degeneration (RD) is an irreversible blinding disease that seriously affects patients’ daily activities and mental health. Targeting hyperactivated microglia regulating polarization are promising strategies for treating the disease. Mesenchymal stem cell (MSC) transplantation proven to be effective treatment due its immunomodulatory regenerative properties. However, low efficiency of migration integration MSCs remains a major obstacle clinical use. The goal this study develop nanodelivery system targets inhibits their release proinflammatory factors, achieve durable neuroprotection. This approach engineer extracellular vesicles (EVs) isolated from MSC, modify them with cyclic RGD (cRGD) peptide on surface, load antagonist IL‐1 receptor, anakinra. Comparing non‐engineered EVs, it observed engineered cRGD‐EVs exhibit increased targeting against strongly protected photoreceptors in experimental RD cells animal models. provides strategy improve drug delivery degenerated retinas offers through targeted modulation immune microenvironment via cRGD‐EVs.

Language: Английский

Citations

18

Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model DOI
Y. Jin,

Danyang Cai,

Li‐Hua Mo

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 309, P. 122617 - 122617

Published: May 17, 2024

Language: Английский

Citations

7