气候变化领域集成服务门户(CCPortal): Agonist of growth hormone–releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury

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DOI	10.1073/pnas.1920834118
	Agonist of growth hormone–releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury
	Cen L.-P.; Ng T.K.; Liang J.-J.; Xu C.; Zhuang X.; Liu Y.-F.; Chen S.-L.; Xu Y.; Yang Q.; Yuan X.-L.; Qin Y.J.; Chan S.O.; Chen H.; Zhang M.; Schally A.V.; Pang C.P.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:28
英文摘要	Optic neuropathies are leading causes of irreversible visual impairment and blindness, currently affecting more than 100 million people worldwide. Glaucoma is a group of optic neuropathies attributed to progressive degeneration of retinal ganglion cells (RGCs). We have previously demonstrated an increase in survival of RGCs by the activation of macrophages, whereas the inhibition of macrophages was involved in the alleviation on endotoxin-induced inflammation by antagonist of growth hormone–releasing hormone (GHRH). Herein, we hypothesized that GHRH receptor (GHRH-R) signaling could be involved in the survival of RGCs mediated by inflammation. We found the expression of GHRH-R in RGCs of adult rat retina. After optic nerve crush, subcutaneous application of GHRH agonist MR-409 or antagonist MIA-602 promoted the survival of RGCs. Both the GHRH agonist and antagonist increased the phosphorylation of Akt in the retina, but only agonist MR-409 promoted microglia activation in the retina. The antagonist MIA-602 reduced significantly the expression of inflammation-related genes Il1b, Il6, and Tnf. Moreover, agonist MR-409 further enhanced the promotion of RGC survival by lens injury or zymosan-induced macrophage activation, whereas antagonist MIA-602 attenuated the enhancement in RGC survival. Our findings reveal the protective effect of agonistic analogs of GHRH on RGCs in rats after optic nerve injury and its additive effect to macrophage activation, indicating a therapeutic potential of GHRH agonists for the protection of RGCs against optic neuropathies especially in glaucoma. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	GHRH; Macrophage activation; Neuroprotection; Optic nerve injury; Retinal ganglion cells
语种	英语
scopus关键词	growth hormone releasing factor; interleukin 1beta; interleukin 6; protein kinase B; tumor necrosis factor; zymosan; GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-; growth hormone; growth hormone releasing factor; hormone receptor; N-Me-Tyr1,D-Ala2,Asn8,Arg29-NHCH3-JI-38; neuropeptide receptor; phosphatidylinositol 3 kinase; protein kinase B; sermorelin; somatotropin releasing hormone receptor; STAT3 protein; zymosan; adult; animal experiment; animal model; Article; cell protection; cell survival; controlled study; glaucoma; human; inflammation; macrophage; macrophage activation; MAPK signaling; nonhuman; optic nerve disease; optic nerve injury; phosphorylation; Pi3K/Akt signaling; rat; retina; retina ganglion cell; signal transduction; young adult; animal; drug effect; Fischer 344 rat; gene expression regulation; genetics; macrophage; male; metabolism; microglia; neuroprotection; optic nerve injury; pathology; retina ganglion cell; vitreous body; Animals; Cell Survival; Gene Expression Regulation; Growth Hormone; Growth Hormone-Releasing Hormone; Inflammation; Macrophages; Male; MAP Kinase Signaling System; Microglia; Neuroprotection; Optic Nerve Injuries; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats, Inbred F344; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; Retinal Ganglion Cells; Sermorelin; Signal Transduction; STAT3 Transcription Factor; Vitreous Body; Zymosan
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251126
作者单位	Joint Shantou International Eye Center of Shantou University, Chinese University of Hong Kong, Shantou University Medical College, Shantou, 515041, China; Shantou University Medical College, Shantou, 515041, China; Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong; Department of Ophthalmology, Guangdong Eye Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong; Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, United States; Division of Medical Oncology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, United States; Division of Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, United States; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, United State...
推荐引用方式 GB/T 7714	Cen L.-P.,Ng T.K.,Liang J.-J.,等. Agonist of growth hormone–releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury[J],2021,118(28).
APA	Cen L.-P..,Ng T.K..,Liang J.-J..,Xu C..,Zhuang X..,...&Pang C.P..(2021).Agonist of growth hormone–releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury.Proceedings of the National Academy of Sciences of the United States of America,118(28).
MLA	Cen L.-P.,et al."Agonist of growth hormone–releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury".Proceedings of the National Academy of Sciences of the United States of America 118.28(2021).