Melanocortins applied intravitreally delay retinal dystrophy in Royal College of Surgeons rats

Naveh, Nava

doi:10.1007/s00417-003-0781-y

Cited by 20 publications

(16 citation statements)

References 32 publications

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“…For example, α-MSH suppresses inflammation and maintains an intact retina in infectious [20] and autoimmune [21] uveitis, respectively. Intravitreal injection of an α-MSH analog protects photoreceptor cells from death in a rat model of retinal dystrophy in a dose-dependent manner [22]. It is also notable that α-MSH suppresses the oxidative stress induced by ultraviolet radiation in skin keratinocytes and melanocytes via the MC1R-mediated cAMP-PKA pathway, independent of melanin genesis [23]–[25].…”

Section: Introductionmentioning

confidence: 99%

α-Melanocyte-Stimulating Hormone Protects Retinal Vascular Endothelial Cells from Oxidative Stress and Apoptosis in a Rat Model of Diabetes

et al. 2014

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AimsOxidative stress and apoptosis are among the earliest lesions of diabetic retinopathy. This study sought to examine the anti-oxidative and anti-apoptotic effects of α-melanocyte-stimulating hormone (α-MSH) in early diabetic retinas and to explore the underlying mechanisms in retinal vascular endothelial cells.MethodsSprague-Dawley rats were injected intravenously with streptozocin to induce diabetes. The diabetic rats were injected intravitreally with α-MSH or saline. At week 5 after diabetes, the retinas were analyzed for reactive oxygen species (ROS) and gene expression. One week later, the retinas were processed for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and transmission electron microscopy. Retinal vascular endothelial cells were stimulated by high glucose (HG) with or without α-MSH. The expression of Forkhead box O genes (Foxos) was examined through real-time PCR. The Foxo4 gene was overexpressed in endothelial cells by transient transfection prior to α-MSH or HG treatment, and oxidative stress and apoptosis were analyzed through CM-H2DCFDA and annexin-V assays, respectively.ResultsIn diabetic retinas, the levels of H2O2 and ROS and the total anti-oxidant capacity were normalized, the apoptotic cell number was reduced, and the ultrastructural injuries were ameliorated by α-MSH. Treatment with α-MSH also corrected the aberrant changes in eNOS, iNOS, ICAM-1, and TNF-α expression levels in diabetic retinas. Furthermore, α-MSH inhibited Foxo4 up-regulation in diabetic retinas and in endothelial cells exposed to HG, whereas Foxo4 overexpression abrogated the anti-oxidative and anti-apoptotic effects of α-MSH in HG-stimulated retinal vascular endothelial cells.Conclusionsα-MSH normalized oxidative stress, reduced apoptosis and ultrastructural injuries, and corrected gene expression levels in early diabetic retinas. The protective effects of α-MSH in retinal vascular endothelial cells may be mediated through the inhibition of Foxo4 up-regulation induced by HG. This study suggests an α-MSH-mediated potential intervention approach to early diabetic retinopathy and a novel regulatory mechanism involving Foxo4.

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Section: Introductionmentioning

confidence: 99%

α-Melanocyte-Stimulating Hormone Protects Retinal Vascular Endothelial Cells from Oxidative Stress and Apoptosis in a Rat Model of Diabetes

et al. 2014

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“…Intravitreal injection of α-MSH analogs retard photoreceptor loss in RCS rat, which is a model of retinal dystrophy. 71 This may be working through the melanocortin receptors inducing some undefined neurotropic activity. It has also been demonstrated that topical application of α-MSH is effective in lowering the intraocular pressure in normal tension rabbits for up to six hours by stimulating PGE2 and prostacyclin levels in iris and ciliary body cells.…”

Section: Application Of α-Msh In Ocular Therapymentioning

confidence: 99%

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

Taylor

Lee

2010

Advances in Experimental Medicine and Biology

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There is an important role for α-MSH and the melanocortin receptors in ocular immunity, development and health. This chapter will cover what is known about how α-MSH is part of the mechanisms of ocular immune privilege, about the expression of melanocortin receptors and the implications of these findings on the role of α-MSH in ocular physiology and its potential use to treat ocular pathologies.

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“…Taylor et al find αMSH is a post-caspase suppressor of apoptosis in macrophages [14]. Intravitreal injection of an αMSH analog protects photoreceptor cells from death in a rat model of retinal dystrophy in a dose-dependent manner [15]. However, few literatures were found in the study of αMSH in adipocyte apoptosis and the regulatory mechanism in the process.…”

Section: Introductionmentioning

confidence: 99%

αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

Cao

et al. 2017

Oncotarget

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Alpha-melanocyte stimulating hormone (αMSH) is an important adenohypophysis polypeptide hormone that regulates body metabolic status. To date, it is well known that the disorder of hypothalamic αMSH secretion is related to many metabolic diseases, such as obesity and type II diabetes. However, the underlying mechanisms are poorly understood. In our study, we focused on the reactive oxygen species (ROS)-induced adipocyte apoptosis and tried to unveil the role of αMSH in this process and the signal pathway which αMSH acts through. Kunming white mice were used and induced to oxidative stress status by hydrogen peroxide (H2O2) injection and a significant reduction of αMSH were found in mice serum, while elevated ROS level and mRNA level of pro-apoptotic genes were observed in mice adipose tissue. What is more, when detect the function of αMSH in ROS-induced apoptosis, similar inhibitory trend was found with the oxidative stress inhibitor N-acetyl-L-cysteine (NAC) in ROS-induced adipocyte apoptosis and this trend is αMSH receptor melanocortin 5 receptor (MC5R) depended, while an opposite trend was found between αMSH and Foxo1, which is a known positive regulator of adipocyte apoptosis. Further, we found that the repress effect of αMSH in adipocytes apoptosis is acting through Foxo1/mTORC2 pathway. These findings indicate that, αMSH has a strong inhibitory effect on ROS-induced adipocyte apoptosis and underlying mechanism is interacting with key factors in mTOR signal pathway. Our study demonstrated a great role of αMSH in adipocyte apoptosis and brings a new therapeutic mean to the treatment of obesity and diabetes.

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Melanocortins applied intravitreally delay retinal dystrophy in Royal College of Surgeons rats

Cited by 20 publications

References 32 publications

α-Melanocyte-Stimulating Hormone Protects Retinal Vascular Endothelial Cells from Oxidative Stress and Apoptosis in a Rat Model of Diabetes

α-Melanocyte-Stimulating Hormone Protects Retinal Vascular Endothelial Cells from Oxidative Stress and Apoptosis in a Rat Model of Diabetes

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

αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

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