Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects
Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects
复制标题
DOI：
10.1111/j.1749-6632.2010.05512.x
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Reglodi, D.
中科院分区：
文献类型：
--
作者：
Atlasz, T.;Szabadfi, K.;Reglodi, D.
垂体腺苷酸环化酶激活多肽（垂体腺苷酸环化酶激活多肽，PACAP）是一种神经营养肽和神经保护肽，已被证明对不同的神经元损伤，如创伤性脑和脊髓损伤、神经退行性疾病模型和脑缺血发挥保护作用。PACAP及其受体存在于视网膜中。本文综述了目前有关视网膜PACAP的研究进展，重点介绍了其对视网膜的保护作用。综述了组织、免疫组织化学和分子生物学分析的结果。在体外，PACAP显示出对谷氨酸、谷氨酰胺、大霉素和缺氧的保护作用。在体内，玻璃体内PACAP治疗的保护作用已在以下大鼠视网膜变性模型中得到证实：谷氨酸和海因酸盐引起的兴奋性毒性损伤、缺血性损伤、UV-A光引起的变性、视神经横断和链脲霉素引起的糖尿病性视网膜病变。通过对其分子机制的研究发现，PACAP在体内通过激活视网膜的抗凋亡和抑制促凋亡信号通路发挥作用。这些研究强烈提示PACAP是一种极好的候选视网膜保护剂，可能成为各种视网膜疾病的潜在治疗物质。
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects against different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors are present in the retina. In this study, we summarize the current knowledge on retinal PACAP with focus on the retinoprotective effects. Results of histological, immunohistochemical, and molecular biological analysis are reviewed. In vitro, PACAP shows protection against glutamate, thapsigargin, anisomycin, and anoxia. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models of retinal degeneration in rats: excitotoxic injury induced by glutamate and kainate, ischemic injury, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy. Studying the molecular mechanism has revealed that PACAP acts by activating antiapoptotic and inhibiting proapoptotic signaling pathways in the retina in vivo. These studies strongly suggest that PACAP is an excellent candidate retinoprotective agent that could be a potential therapeutic substance in various retinal diseases.