Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 24, 2024

Abstract Ischemic retinopathies including diabetic retinopathy are major causes of vision loss. Inner blood-retinal barrier (BRB) breakdown with retinal vascular hyperpermeability results in macular edema. Although dysfunction the neurovascular unit neurons, glia, and cells is now understood to underlie this process, there a need for fuller elucidation underlying events BRB ischemic disease, systematic analysis myeloid exploration cellular cross-talk. We used an approach microglia depletion CSF-1R inhibitor PLX5622 (PLX) ischemia-reperfusion (IR) model. Under non-IR conditions, PLX treatment successfully depleted retina. suppressed microglial activation response following IR as well infiltration monocyte-derived macrophages. This occurred association reduction expression chemokines CCL2 inflammatory adhesion molecule ICAM-1 . In addition, was marked suppression neuroinflammation IL-1b , IL-6 Ptgs2 TNF-a Angpt2 protein that regulates permeability. significantly inner IR, without appreciable effect on neuronal dysfunction. A translatomic Müller glial-specific gene vivo using Ribotag demonstrated strong cell multiple pro-inflammatory genes treatment. Co-culture studies activated directly upregulates cell-expression these genes, indicating downstream effector IR. two types endothelial ability both compromise EC function. Interestingly, quiescent enhanced function co-culture system. Together demonstrates pivotal role setting ischemia-associated disease indicates play iBRB dysregulation, through direct indirect effects, while glia participate amplifying neuroinflammatory cells.

Язык: Английский

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Role of inflammation in a rat model of radiation retinopathy

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Июнь 24, 2024

Abstract Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids laser photocoagulation have limited effects on RR. The role retinal inflammation its contribution the microvascular damage occurring remain incompletely understood. To explore cellular vascular events after irradiation, we analyzed their time course at 1 week, month 6 months rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes microglia were rapidly activated, these markers persisted for irradiation. This was accompanied early cell death outer retina, which later points, thinning. A loss small capillaries hypoxia observed months, indicating inner blood‒retinal barrier (BRB) alteration but without retina. Moreover, activated microglial cells invaded entire retina surrounded vessels, suggesting death. also triggered persistent invasion pigment epithelium macrophages, contributing BRB disruption. study highlights long-lasting inflammatory mechanisms development demonstrates relevance this model investigate human pathology.

Язык: Английский

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Ganoderma lucidum polysaccharide attenuates retinal ischemia-reperfusion injury by regulating microglial M1/M2 polarization, suppressing neuroinflammation and inhibiting JAK2/STAT3 pathway

Biochemistry and Biophysics Reports, Год журнала: 2025, Номер 41, С. 101926 - 101926

Опубликована: Янв. 29, 2025

Язык: Английский

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Current Opportunities and Future Prospects of Neuroprotective Therapy in Glaucoma. Literature Review. Part 1

Ophthalmology in Russia, Год журнала: 2025, Номер 22(1), С. 5 - 15

Опубликована: Март 28, 2025

This literature review is devoted to one of the most complex ophthalmology problems — neuroprotective and neuroregenerative treatment glaucoma consists two parts. The first part considers main mechanisms neurodegeneration aspects therapeutic control related these (excitotoxicity, mitochondrial dysfunction, oxidative stress). aim conducted analysis provide a comprehensive overview both existing strategies promising areas therapy based on agents in potential glaucoma. A wide range approaches neuroprotection demonstrates great for effective order preserve visual functions patients with

Язык: Английский

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Study on the Protective Effects and Mechanisms of Atorvastatin in Retinal Ischemia-Reperfusion Injury in Mice

Опубликована: Янв. 1, 2025

Язык: Английский

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Roflumilast Attenuates Microglial Senescence and Retinal Inflammatory Neurodegeneration Post Retinal Ischemia Reperfusion Injury Through Inhibiting NLRP3 Inflammasome

Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(12), С. 38 - 38

Опубликована: Окт. 24, 2024

Retinal ischemia-reperfusion (RIR) injury is implicated in various retinal diseases, leading to ganglion cells (RGCs) degeneration. Microglial senescence exacerbates inflammation, contributing neurodegeneration. This study aimed investigate the potential therapeutic role of Roflumilast (Roflu) ameliorating microglial and neuroinflammation following RIR injury.

Язык: Английский

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