磷酸二酯酶抑制剂调控小胶质细胞活化治疗青光眼的研究进展  

Advances of phosphodiesterase inhibitor in microglia-medicated immunomodulatory effects as new anti-glaucoma drugs

作　　者：王雪婷 党亚龙[2] 魏菁[1] 雷方[3] WANG Xueting;DANG Yalong;WEI Jing;LEI Fang(Department of Ophthalmology,the First Affiliated Hospital of Henan University of Science and Technology,College of Clinical Medicine of Henan University of Science and Technology,Luoyang 471003,Henan Province,China;Sanmenxia Center Hospital Affiliated to Henan University of Science and Technology,Sanmenxia Eye Hospital,Sanmenxia 472000,Henan Province,China;Henan University of Science and Technology,Luoyang 471000,Henan Province,China)

机构地区：[1]河南科技大学临床医学院,河南科技大学第一附属医院眼科,河南省洛阳市471003 [2]河南科技大学附属三门峡市中心医院,三门峡市眼科医院,河南省三门峡市472000 [3]河南科技大学,河南省洛阳市471000

出　　处：《眼科新进展》2021年第2期194-200,共7页Recent Advances in Ophthalmology

基　　金：河南省重点研发与推广专项(编号182102410099)。

摘　　要：青光眼是世界上发病率最高的不可逆致盲性眼病,主要表现为进行性的视网膜神经节细胞死亡、视神经萎缩和视野缺损。青光眼性神经节细胞死亡的机制复杂,小胶质细胞过度活化是重要因素之一。环磷酸腺苷(cAMP)与小胶质细胞活化密切相关。一方面,细胞浆内cAMP水平升高可以通过活化PKA/CREB信号通路抑制核因子κB的转录,从而减少小胶质细胞炎症介质的转录和释放。另一方面,cAMP也能上调小胶质细胞IL-10等神经营养因子的表达。磷酸二酯酶抑制剂能够抑制cAMP水解,提高细胞浆cAMP水平,目前广泛应用于外周小动脉缺血、阳痿等多种疾病,其免疫调节作用尚未深入探讨。作者前期研究表明,罂粟碱等磷酸二酯酶抑制剂能够有效抑制视网膜小胶质细胞炎症,保护神经节细胞。本文就磷酸二酶酶抑制剂通过调控小胶质细胞活化治疗青光眼的研究进展进行综述。Glaucoma is the leading cause of irreversible blindness worldwide.Progressive death of retinal ganglion cells,atrophy of the optic nerve and defect of visual field are its characteristics.The mechanism of the glaucomatous retina canglion cell(RGC)death is very complicated,and over activation of microglia is one of the major causes.cAMP and microglia activation are closely related.On the one hand,elevation of cytosolic cAMP can inhibit the activation of NF-κB signal by activating PKA/CREB signaling pathway,thus reduce the transcription and expression of inflammatory mediators.On the other hand,cAMP can also up-regulate the expression of neurotrophic factors such as IL-10 in microglia.Phosphodiesterase inhibitors can inhibit the hydrolysis of cAMP and increase the concentration of cytosolic cAMP.It is widely used in peripheral arterial ischemia,impotence and other diseases;however,its immunomodulatory effects have not been further investigated.Our previous studies have shown that phosphodiesterase inhibitors such as papaverine can effectively inhibit the inflammation of retinal microglia and protect retinal ganglion cells.In this review,we will summarize the recent advances of using phosphodiesterase inhibitor in microglia-medicated immunomodulatory effects.

关 键 词：小胶质细胞 环磷酸腺苷 磷酸二酯酶抑制剂 炎症 

分 类 号：R775.9[医药卫生—眼科]