Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Fu, Xuefei; Feng, Shuyu; Qin, Huan; Lin, Yan; Zheng, Caiyan; Yao, Kai

doi:10.3389/fnmol.2023.1100254

Cited by 21 publications

(8 citation statements)

References 229 publications

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“…Indeed, we observed an increase in the total microglia population (CD11b high ; CD45 low ; Ly6G - ; Ly6C - ; F4/80 mid ] in the db/db mice. Consistent with previous studies (Fu et al, 2023; Hu et al, 2017), while there was a decrease in resident microglial populations, this difference was not statistically significant. We speculate this may be due to the duration of diabetes, analysis type (immunofluorescence vs. flow cytometry), and sample size.…”

Section: Discussionsupporting

confidence: 91%

Transcriptomic Profile of Lin^-Sca1⁺c-kit (LSK) cells in db/db mice with long-standing diabetes

Mahajan,

Luo,

Abhyankar

et al. 2024

Preprint

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The Lin-Sca1+c-Kit+ (LSK) fraction comprises multipotent hematopoietic stem cells (HSCs), vital to tissue homeostasis and vascular repair. While HSC homeostasis is impaired in diabetes, it is not known how chronic (>6 months) type 2 diabetes (T2D) alters the HSC transcriptome. Herein, we assessed the transcriptomic signature of HSCs in db/db mice employing mRNA and miRNA sequencing. We uncovered 2076 mRNAs and 35 miRNAs differentially expressed in db/db mice, including two novel miRNAs previously unreported in T2D. Further analysis of these transcripts showed a molecular shift with an increase in the pro-inflammatory cytokines and a decrease in anti-inflammatory cytokine expression. Also, pathway mapping unveiled inflammation and angiogenesis as one of the top pathways. These effects were reflected in bone marrow mobilopathy, retinal microglial inflammation, and neurovascular deficits in db/db mice. In conclusion, our study highlights that chronic diabetes alters HSCs at the transcriptomic level, thus potentially contributing to overall homeostasis and neurovascular deficits of diabetes, such as diabetic retinopathy.

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Section: Discussionsupporting

confidence: 91%

Transcriptomic Profile of Lin^-Sca1⁺c-kit (LSK) cells in db/db mice with long-standing diabetes

Mahajan,

Luo,

Abhyankar

et al. 2024

Preprint

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“…Indeed, benzodiazepines activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO) that is expressed in activated micro‐ and macroglial cells. Retinal micro‐ and macroglia activation can lead to increased production of angiogenic (VEGF, Ang‐2) and proinflammatory mediators (IL‐6, IL‐8, IL‐10, MCP‐1, PDGF‐A) and increase DME (Fu et al, 2023). Many drugs structurally related to diazepam also bind to a benzodiazepine TSPO receptor.…”

Section: Discussionmentioning

confidence: 99%

Development of diabetic macular oedema shows associations with systemic medication – An epidemiological study

Loukovaara,

Korhonen,

Niskanen

et al. 2023

Acta Ophthalmologica

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PurposeTo identify associations between systemic drugs and the incidence of diabetic macular oedema (DME). Of interest was to find beneficial and/or deleterious associations of used drugs.MethodsA historic cohort design based on administrative data. Study population consisted of 150 353 individuals with diabetes. Endpoint event was the development of DME (ICD‐10 H36.01), censoring events were death or study end December 2017. The follow‐up started between 1997 and 2010. The systemic medication consisted of 95 substances. We constructed a nested case–control study design comparing 2630 cases with DME to 13 144 age‐ and sex‐matched controls without DME. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) based on conditional logistic regression models.ResultsIncidence rate for DME was 1.80 per 1000 person‐years (95% CI 1.73–1.87). In all, we observed a lower incidence rate of DME in females (IRR 0.57; 95% CI 0.52–0.62) compared to males. Exposure to hormone replacement therapy estradiol (OR 0.42; 0.25–0.68), temazepam (0.23; 0.08–0.62) and allopurinol (0.61; 0.43–0.86) were associated with lower risk of DME, while use of insulin or insulin analogue (3.30; 2.99–3.64), sulfonylureas (1.21; 1.05–1.40), diuretic furosemide (1.90; 1.61–2.24), calcium channel blocker amlodipine (1.53; 1.34–1.75), ACE inhibitors ramipril (1.66; 1.46–1.89) and enalapril (1.38; 1.16–1.64) were associated with an increased risk of DME.ConclusionsLarge‐scale studies examining the incidence of DME are lacking. Our findings suggest that associations of systemic medications with the incidence of DME may shed light on the pathogenesis of complex DME, encouraging further studies.

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“…Chronic inflammation by further recruiting and activating microglia would facilities the neointimal growth toward the retina [ 60 ]. the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea) [ 61 ].…”

Section: Molecular Mechanisms Of Microglia Involvement In Amdmentioning

confidence: 99%

Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

2024

Aging dis

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Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to the activation of resident microglia. The migration of activated microglia to the ongoing retinal lesion and their morphological transformation from branching to ameboid-like are recognized as hallmarks of AMD pathogenesis. Activated microglia send signals to Müller cells and promote them to react correspondingly to damaging stimulus. Müller cells are a type of neuroglia cells that maintain the normal function of retinal neurons, modulating innate inflammatory responses, and stabilize retinal structure. Activated Müller cells can accelerate the progression of AMD by damaging neurons and blood vessels. Therefore, the crosstalk between microglia and Müller cells plays a homeostatic role in maintaining the retinal environment, and this interaction is complicatedly modulated. In particular, the mechanism of mutual regulation between the two glia populations is complex under pathological conditions. This paper reviews recent findings on the crosstalk between microglia and Müller glia during AMD pathology process, with special emphasis on its therapeutic potentials.

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Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Cited by 21 publications

References 229 publications

Transcriptomic Profile of Lin^-Sca1⁺c-kit (LSK) cells in db/db mice with long-standing diabetes

Transcriptomic Profile of Lin^-Sca1⁺c-kit (LSK) cells in db/db mice with long-standing diabetes

Development of diabetic macular oedema shows associations with systemic medication – An epidemiological study

Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

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Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Cited by 21 publications

References 229 publications

Transcriptomic Profile of Lin-Sca1+c-kit (LSK) cells in db/db mice with long-standing diabetes

Transcriptomic Profile of Lin-Sca1+c-kit (LSK) cells in db/db mice with long-standing diabetes

Development of diabetic macular oedema shows associations with systemic medication – An epidemiological study

Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

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Transcriptomic Profile of Lin^-Sca1⁺c-kit (LSK) cells in db/db mice with long-standing diabetes

Transcriptomic Profile of Lin^-Sca1⁺c-kit (LSK) cells in db/db mice with long-standing diabetes