Intraocular Delivery of miR-146 Inhibits Diabetes-Induced Retinal Functional Defects in Diabetic Rat Model

Zhuang, Pei; Muraleedharan, Chithra; Xu, Shunbin

doi:10.1167/iovs.16-21223

Cited by 50 publications

(37 citation statements)

References 98 publications

(138 reference statements)

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“…Western blot was performed following a standard protocol as we described previously [24]. Briefly, the protein lysate from Raw cells was homogenized using a pellet pestle motor (Fisher Scientific, Chicago, IL, USA) in RIPA buffer with a protease inhibitor cocktail, including 0.5 μM 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF); 0.4 μM aprotinin, 10 μM leupeptin, 20 μM bestatin, 7.5 μM pepstatin A, and 7.0 μM E-64 (Sigma).…”

Section: Methodsmentioning

confidence: 99%

The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to Pseudomonas aeruginosa

et al. 2019

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Macrophages (Mϕ) are an important component of the innate immune system; they play critical roles in the first line of defense to pathogen invasion and modulate adaptive immunity. MicroRNAs (miRNAs) are a newly recognized, important level of gene expression regulation. However, their roles in the regulation of Mϕ and the immune system are still not fully understood. In this report, we provide evidence that the conserved miR-183/96/182 cluster (miR-183/96/182) modulates Mϕ function in their production of reactive nitrogen (RNS) and oxygen species (ROS) and their inflammatory response to Pseudomonas aeruginosa (PA) infection and/or lipopolysaccharide (LPS) treatment. We show that knockdown of miR-183/96/182 results in decreased production of multiple proinflammatory cytokines in response to PA or LPS treatment in Mϕ-like Raw264.7 cells. Consistently, peritoneal Mϕ from miR-183/96/182-knockout versus wild-type mice are less responsive to PA or LPS, although their basal levels of proinflammatory cytokines are increased. In addition, overexpression of miR-183/96/182 results in decreased production of nitrite and ROS in Raw264.7 cells. We also provide evidence that DAP12 and Nox2 are downstream target genes of miR-183/96/182. These data suggest that miR-183/96/182 imposes global regulation on various aspects of Mϕ function through different downstream target genes.

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Section: Methodsmentioning

confidence: 99%

The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to Pseudomonas aeruginosa

et al. 2019

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“…Finally, since intraocular injection is a frequently used treatment in a number of ocular pathologies [35,36], our study makes an important contribution by showing that this procedure is also able to modulate subcortical connections. In this scenario, the delivery of anti-inflammatory agents by intravitreous injection is emerging as a promising tool to help the recovery of inflammation-mediated lesions in the developing CNS.…”

Section: Discussionmentioning

confidence: 74%

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Goulart¹,

Menezes²,

Espírito-Santo³

et al. 2018

Neuroimmunomodulation

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Objective: Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to different aspects of central nervous system development such as survival, proliferation, and differentiation, among others. Our goals were to investigate the effect of intravitreous treatment with IL-4 on the activation of downstream signaling pathways in the retina and the distribution of retinal axons within the superior colliculus (SC). Material and Methods: Lister hooded rats were submitted to an intravitreous injection of either IL-4 (5 U/µL) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western blot or immunohistochemistry. At PND13, a group of animals received an intraocular injection of an anterograde tracer in the left (untreated) eye in order to label the uncrossed retinotectal axons. Results: Our data revealed that intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content and a sustained increase in the phosphorylation of STAT6 and ERK levels in the retina. IL-4 also increases retinal axonal arbors within the SC, compared to control groups. Conclusions: These data suggest that a single in vivo treatment with IL-4 during the early stages of development modulates signaling pathways in the retina, resulting in altered binocular subcortical visual connectivity.

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“…Upregulation of miR-146a exerts negative regulation in multiple pathways of NF-κB activation, which suggests its correlation to inflammatory responses in DR [148,[192][193][194][195][196][197]. Specifically, miR-146a upregulates inflammatory cytokines in the diabetic retina and kidney [197], protects HRMECs [194], reduces retinal microvascular leakage, and improves visual function in diabetic rats [198]. Moreover, diabetes induces rhythmic dysregulation of miR-146a and its inflammatory genes in human retinal endothelial cells [195].…”

Section: Mir-146amentioning

confidence: 99%

MicroRNAs in Vascular Eye Diseases

Liu

Huang

Britton

et al. 2020

IJMS

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Since the discovery of the first microRNA (miRNA) decades ago, studies of miRNA biology have expanded in many biomedical research fields, including eye research. The critical roles of miRNAs in normal development and diseases have made miRNAs useful biomarkers or molecular targets for potential therapeutics. In the eye, ocular neovascularization (NV) is a leading cause of blindness in multiple vascular eye diseases. Current anti-angiogenic therapies, such as anti-vascular endothelial growth factor (VEGF) treatment, have their limitations, indicating the need for investigating new targets. Recent studies established the roles of various miRNAs in the regulation of pathological ocular NV, suggesting miRNAs as both biomarkers and therapeutic targets in vascular eye diseases. This review summarizes the biogenesis of miRNAs, and their functions in the normal development and diseases of the eye, with a focus on clinical and experimental retinopathies in both human and animal models. Discovery of novel targets involving miRNAs in vascular eye diseases will provide insights for developing new treatments to counter ocular NV.

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Intraocular Delivery of miR-146 Inhibits Diabetes-Induced Retinal Functional Defects in Diabetic Rat Model

Abstract: Citation: Zhuang P, Muraleedharan CK, Xu S. Intraocular delivery of miR-146 inhibits diabetes-induced retinal functional defects in diabetic rat model. Invest Ophthalmol Vis Sci.

Cited by 50 publications

References 98 publications

The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to <b><i>Pseudomonas aeruginosa</i></b>

The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to <b><i>Pseudomonas aeruginosa</i></b>

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

MicroRNAs in Vascular Eye Diseases

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