Stimulating the Melanocortin System in Uveitis and Diabetes Preserves the Structure and Anti-Inflammatory Activity of the Retina.
Stimulating the Melanocortin System in Uveitis and Diabetes Preserves the Structure and Anti-Inflammatory Activity of the Retina.
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DOI：
10.3390/ijms24086928
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发表时间：
2023-04-08
影响因子：
5.6
通讯作者：
Taylor, Andrew W.
中科院分区：
文献类型：
--
作者：
Ng, Tat Fong;Taylor, Andrew W.
关键词：
内源性神经肽α-黑素细胞刺激激素（α-MSH）是一种有效的炎症抑制剂，在维持视网膜正常的抗炎微环境中起重要作用。虽然已经证明了α-MSH肽在葡萄膜炎和糖尿病视网膜病变模型中的治疗用途，但其短半衰期和不稳定性限制了其作为治疗药物的用途。类似物PL-8331对黑皮质素受体具有更强的亲和力，半衰期更长，并且到目前为止与α-MSH功能相同，具有提供基于黑皮质素的治疗的潜力。我们研究了PL-8331对两种视网膜疾病小鼠模型，实验性自身免疫性葡萄膜视网膜炎（EAU）和糖尿病视网膜病变（DR）的影响。应用PL-8331治疗患有EAU的小鼠抑制EAU并保留视网膜结构。在糖尿病小鼠中，PL-8331增强了视网膜细胞的存活并抑制了视网膜中VEGF的产生。此外，来自PL-8331处理的糖尿病小鼠的视网膜色素上皮细胞（RPE）保留了正常的抗炎活性。结果表明，泛黑皮质素受体激动剂PL-8331是一种有效的治疗药物，可以抑制炎症，预防视网膜变性，并保持RPE的正常抗炎活性。
The endogenous neuropeptide α-Melanocyte Stimulating Hormone (α-MSH) is a potent suppressor of inflammation and has an essential role in maintaining the normal anti-inflammatory microenvironment of the retina. While the therapeutic use of α-MSH peptide in uveitis and diabetic retinopathy models has been demonstrated, its short half-life and instability limit its use as a therapeutic drug. A comparable analog, PL-8331, which has a stronger affinity to melanocortin receptors, longer half-life, and, so far, is functionally identical to α-MSH, has the potential to deliver melanocortin-based therapy. We examined the effects of PL-8331 on two mouse models of retinal disease, Experimental Autoimmune Uveoretinitis (EAU) and Diabetic Retinopathy (DR). PL-8331 therapy applied to mice with EAU suppressed EAU and preserved retinal structures. In diabetic mice, PL-8331 enhanced the survival of retinal cells and suppressed VEGF production in the retina. In addition, retinal pigment epithelial cells (RPE) from PL-8331-treated diabetic mice retained normal anti-inflammatory activity. The results demonstrated that the pan-melanocortin receptor agonist PL-8331 is a potent therapeutic drug to suppress inflammation, prevent retinal degeneration, and preserve the normal anti-inflammatory activity of RPE.
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影响因子：
3.4
作者：
Ng, Tat Fong;Dawit, Kaleb;Taylor, Andrew W.
通讯作者：
Taylor, Andrew W.
影响因子：
4.3
作者：
Goit RK;Taylor AW;Lo ACY
通讯作者：
Lo ACY
影响因子：
3.7
作者：
Taylor AW
通讯作者：
Taylor AW
影响因子：
2.3
作者：
Nelson, Winnie W.;Lima, Antonio Flavio;Carroll, Susan
通讯作者：
Carroll, Susan
影响因子：
3.3
作者：
Edling, Andrea E.;Gomes, Danilo;Perricone, Michael A.
通讯作者：
Perricone, Michael A.