Localized retinal neuropeptide regulation of macrophage and microglial cell functionality

Kawanaka, Norikuni; Taylor, Andrew W.

doi:10.1016/j.jneuroim.2010.09.025

Cited by 42 publications

(119 citation statements)

References 43 publications

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“…Antibody concentrations were 2 μg/ml, a level that would bind a molar equivalent of 1 mg of α-MSH and NPY. This far in excess of what has been measured in culture for RPE eyecups [4]. The conditioned media with antibody was incubated 1 hour at 37°C.…”

Section: Depletion Of α-Msh and Npymentioning

confidence: 96%

“…Eyecups with intact RPE monolayers were prepared as previously described [1,3,4]. In brief, eyes from euthanized healthy C57BL/6J mice were enucleated, placed in ice cold DMEM (Lonza, Walkersvile, PA), where external muscles, and connective tissue were cut from the eyes.…”

Section: Rpe Eyecupsmentioning

confidence: 99%

“…These two neuropeptides are responsible for RPE inducing characteristics of myeloid suppressor cells in macrophages, and promoting the same characteristics in retinal microglial cells [4]. A part of this suppression is the α-MSH and NPY modulating phagocytic activity in macrophages [6].…”

Section: Introductionmentioning

confidence: 99%

“…This involves regulating the resident, and infiltrating immune cells within the ocular tissues. One of the immunosuppressive mechanisms is mediated by a specific set of soluble neuropeptides, and growth factors found in aqueous humor, and produced by retinal pigment epithelial cells (RPE) [1][2][3][4][5]. Macrophages stimulated to mediate inflammation are suppressed when treated with aqueous humor, or to the soluble factors made by a healthy RPE monolayer.…”

Section: Introductionmentioning

confidence: 99%

“…Two of the soluble neuropeptides made by the RPE are alphamelanocyte stimulating hormone (α-MSH) and neuropeptide Y (NPY) [4]. These two neuropeptides are responsible for RPE inducing characteristics of myeloid suppressor cells in macrophages, and promoting the same characteristics in retinal microglial cells [4].…”

Section: Introductionmentioning

confidence: 99%

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Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Taylor

Dixit

2015

IJOES

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The eye is an immune privileged tissue with multiple mechanisms of immunosuppression to protect the light gathering tissues from the damage of inflammation. One of theses mechanisms involves retinal pigment epithelial cell suppression of phagosome activation in macrophages. The objective of this work is to determine if the human RPE cell line ARPE-19 is capable of suppressing the activation of the phagolysosome in macrophages in a manner similar to primary RPE. The conditioned media of RPE eyecups, sub-confluent, just confluent cultures, or established confluent cultures of human ARPE-19 cells were generated. These condition media were used to treat macrophages phagocytizing pHrodo bioparticles. After 24 hours incubation the macrophages were imaged by fluorescent microscopy, and fluorescence was measured. The fluorescent intensity is proportional to the amount of bioparticles phagocytized and are in an activated phagolysosome. The conditioned media of in situ mouse RPE eyecups significantly suppressed the activation of phagolysosome. The conditioned media from cultures of human ARPE-19 cells, grown to sub-confluence (50%) or grown to confluence had no effect on phagolysosome activation. In contrast, the conditioned media from established confluent cultures significantly suppressed phagolysosome activation. The neuropeptides alpha-MSH and NPY were depleted from the conditioned media of established confluent ARPE-19 cell cultures. This depleted conditioned media had diminished suppression of phagolysosome activation while promoting macrophage cell death. In addition, the condition media from cultures of ARPE-19 monolayers wounded with a bisecting scrape was diminished in suppressing phagolysosome activation. This technical report suggests that like primary RPE monolayers, established confluent cultures of ARPE-19 cells produce soluble factors that suppress the activation of macrophages, and can be used to study the molecular mechanisms of retinal immunobiology. In addition, the results further demonstrate the importance of an intact monolayer of RPE cells to modulate immune cell activity within the eye.

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Section: Depletion Of α-Msh and Npymentioning

confidence: 96%

Section: Rpe Eyecupsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Taylor

Dixit

2015

IJOES

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A Glucose‐Responsive Hydrogel Inhibits Primary and Secondary BRB Injury for Retinal Microenvironment Remodeling in Diabetic Retinopathy

Zhou,

Zhao,

Shi

et al. 2024

Advanced Science

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Current diabetic retinopathy (DR) treatment involves blood glucose regulation combined with laser photocoagulation or intravitreal injection of vascular endothelial growth factor (VEGF) antibodies. However, due to the complex pathogenesis and cross‐interference of multiple biochemical pathways, these interventions cannot block disease progression. Recognizing the critical role of the retinal microenvironment (RME) in DR, it is hypothesized that reshaping the RME by simultaneously inhibiting primary and secondary blood–retinal barrier (BRB) injury can attenuate DR. For this, a glucose‐responsive hydrogel named Cu‐PEI/siMyD88@GEMA‐Con A (CSGC) is developed that effectively delivers Cu‐PEI/siMyD88 nanoparticles (NPs) to the retinal pigment epithelium (RPE). The Cu‐PEI NPs act as antioxidant enzymes, scavenging ROS and inhibiting RPE pyroptosis, ultimately blocking primary BRB injury by reducing microglial activation and Th1 differentiation. Simultaneously, MyD88 expression silence in combination with the Cu‐PEI NPs decreases IL‐18 production, synergistically reduces VEGF levels, and enhances tight junction proteins expression, thus blocking secondary BRB injury. In summary, via remodeling the RME, the CSGC hydrogel has the potential to disrupt the detrimental cycle of cross‐interference between primary and secondary BRB injury, providing a promising therapeutic strategy for DR.

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Tissue‐specific production of MicroRNA‐155 inhibits melanocortin 5 receptor‐dependent suppressor macrophages to promote experimental autoimmune uveitis

et al. 2019

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Tissue-specific immune regulation is an important component of the immune response relevant to many areas of immunology. The focus of this study is on tissue-specific mechanisms that contribute to autoimmune uveitis. Precise gene regulation is necessary for the proper expression of an inflammatory or regulatory response. This precision gene regulation can be accomplished by microRNA at the level of the mRNA transcript. miR-155, in particular, has a complicated role in the immune response with positive and negative inflammatory effects. In this work, we identify a decrease in miR-155 in suppressor macrophages and further examine how tissue-specific production of miR-155 impacts experimental autoimmune uveitis. Importantly, we show that eliminating miR-155 expression by the target tissue before initiation reduces disease severity, but elimination of miR-155 after the onset of inflammation does not alter the course of disease. Additionally, expression of miR-155 by the target tissue before initiation is necessary for the induction of regulatory immunity that protects from further autoimmune disease, but not after the onset of inflammation. In summary, we find a MC5r-dependent decrease in miR-155 in postexperimental autoimmune uveitis APC, miR-155 production by the target tissue is necessary for the initiation of autoimmune uveitis, and may have a role in establishing protective regulatory immunity.Keywords: Autoimmunity r Experimental autoimmune uveitis r Macrophages r miR-155Additional supporting information may be found online in the Supporting Information section at the end of the article.

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Localized retinal neuropeptide regulation of macrophage and microglial cell functionality

Cited by 42 publications

References 43 publications

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

A Glucose‐Responsive Hydrogel Inhibits Primary and Secondary BRB Injury for Retinal Microenvironment Remodeling in Diabetic Retinopathy

Tissue‐specific production of MicroRNA‐155 inhibits melanocortin 5 receptor‐dependent suppressor macrophages to promote experimental autoimmune uveitis

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