Applications of the Role of α-MSH in Ocular Immune Privilege

Taylor, Andrew; Lee, Darren J.

doi:10.1007/978-1-4419-6354-3_12

Cited by 31 publications

(24 citation statements)

References 64 publications

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“…These retinal cells express various immune modulators that can suppress myeloid cell (microglia/macrophage) activation via CD200-CD200R [63], or CX3CL1-CX3CR1 [32]), or reduce T cell activation or induce T regulatory cells (Tregs) formation (through thrombospondin-1, TGF-β, CTLA4, CTLA2, [64-69]), or even induce the death of infiltrating immune cells through Fas ligand (FasL) and Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) [70-72]), or suppress complement activation via CD55, CD46, and the decay-acceleration factor (DAF) [73, 74]). In addition, ocular fluids also contain a number of immunoinhibitory molecules such as TGF-β2, neuropeptides such as α-melanocyte-stimulating hormone, and vasoactive intestinal peptide [75, 76]. …”

Section: Retina – An Immune Privileged Tissuementioning

confidence: 99%

“…These retinal cells express various immune modulators that can suppress myeloid cell (microglia/ macrophage) activation via CD200-CD200R [63] or CX3CL1-CX3CR1 [32], reduce T cell activation, induce T regulatory cell formation (through thrombospondin-1, TGF-b, CTLA4, or CTLA2 [64][65][66][67][68][69]), even induce the death of infiltrating immune cells through FasL and TRAIL [70][71][72]), or suppress complement activation via CD55, CD46, and the DAF [73,74]). In addition, ocular fluids contain a number of immunoinhibitory molecules, such as TGF-b2; neuropeptides, such as a-melanocyte-stimulating hormone; and vasoactive intestinal peptide [75,76]. Importantly, despite being an immune-privileged tissue, when the retina suffers from noxious insults, an immune response can still be mounted by a local defense system, involving retinal innate-immune cells and the complement system.…”

Section: Immune Privilege Property Of the Retinamentioning

confidence: 99%

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Parainflammation, chronic inflammation, and age-related macular degeneration

Chen

2015

Journal of Leukocyte Biology

305

260

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Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

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Section: Retina – An Immune Privileged Tissuementioning

confidence: 99%

Section: Immune Privilege Property Of the Retinamentioning

confidence: 99%

Parainflammation, chronic inflammation, and age-related macular degeneration

Chen

2015

Journal of Leukocyte Biology

305

260

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“…Greater understanding of the melanocortin pathway in EAU recovery has the potential to lead to more effective therapies with long-term benefits not only for uveitis but also for other immunologic diseases needing the induction of immune tolerance. 14 This article reports that the dependence on MC5r expression occurs with an APC that mediates regulatory activity in CD4 ϩ effector T cells found in the post-EAU spleen.…”

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confidence: 99%

Following EAU Recovery There Is an Associated MC5r-Dependent APC Induction of Regulatory Immunity in the Spleen

Lee

Taylor

2011

Invest. Ophthalmol. Vis. Sci.

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“…After posttranslational modifications at both termini, α-MSH becomes biologically active and binds to its cognate receptors, melanocortin receptors (MCR) [10, 11], to regulate physiological functions, including body temperature [12] and metabolism [13]. In the eye, the functions of α-MSH include modulating immune responses [14], maintaining immune privileges [15], and inhibiting inflammation [16]. We have shown, in a series of studies that intravitreal injections of α-MSH exert anti-oxidative and anti-apoptotic effects in retinal vessels and neuroretina of streptozotocin (STZ)-induced diabetic rats [17].…”

Section: Introductionmentioning

confidence: 99%

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R

Cai

Yang

Hou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH’s anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Methods: Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH’s anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH’s protection. Results: Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested partial rescue of functional defects by α-MSH in diabetic retinas; and H&E staining revealed significantly increased thickness of all layers in α-MSH-treated diabetic retinas. Mechanistically, α-MSH corrected aberrant transcript and protein expression of pro-inflammatory factor and tight junction genes in the diseased retinas; moreover, it prevented abnormal changes in TEER and permeability in HG-stimulated RF6A cells, and this anti-hyperpermeability was abolished by a universal MCR blocker or an antagonist specific to MC4R. Conclusions: This study showed previously undescribed protective effects of α-MSH on inhibiting BRB breakdown and vascular leakage, improving electrophysiological functions and morphology in early diabetic retinas, which may be due to its down-regulating pro-inflammatory factors and augmenting tight junctions. α-MSH acts predominantly on MC4R to antagonize hyperpermeability in retinal microvessel endothelial cells.

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Applications of the Role of α-MSH in Ocular Immune Privilege

Cited by 31 publications

References 64 publications

Parainflammation, chronic inflammation, and age-related macular degeneration

Parainflammation, chronic inflammation, and age-related macular degeneration

Following EAU Recovery There Is an Associated MC5r-Dependent APC Induction of Regulatory Immunity in the Spleen

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R

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