Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Medical University of South Carolina , Charleston, South Carolina.
J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):119-128. doi: 10.1089/jop.2017.0039.
Since ancient times, opioids have been used clinically and abused recreationally. In the early stages (about 1,000 AD) of opium history, an Arab physician, Avicenna, administered opioids to control diarrhea and eye diseases. Opioids have very strong pain relieving properties and they also regulate numerous cellular responses. Opioid receptors are expressed throughout the body, including the nervous system, heart, lungs, liver, gastrointestinal tract, and retina. Delta opioid receptors (DORs) are a very attractive target from the perspective of both receptor function and their therapeutic potential. Due to a rapid progress in mouse mutagenesis and development of small molecules as DOR agonist, novel functions and roles of DORs have emerged in recent years. This review article focuses on the recent advances in the neuroprotective roles of DOR agonists in general and retina neuroprotection in particular. Rather than being exhaustive, this review highlights the selected studies of DOR function in neuroprotection. We also highlight our preclinical studies using rodent models to demonstrate the potentials of DOR agonists for retinal neuroprotection. Based on existing literature and our recently published data on the eye, DOR agonists possess therapeutic abilities that protect the retina and optic nerve injury against glaucoma and perhaps other retinopathies as well. This review also highlights the signaling events associated with DOR for neuroprotection in the eye. There is a need for translational research on DORs to recognize their potential for clinical application such as in glaucoma.
自古以来，阿片类药物就在临床上被广泛应用，同时也被滥用。在鸦片历史的早期（约公元 1000 年），一位名叫阿维森纳的阿拉伯医生用阿片类药物来控制腹泻和眼部疾病。阿片类药物具有很强的止痛作用，它们还可以调节许多细胞反应。阿片受体在全身表达，包括神经系统、心脏、肺、肝脏、胃肠道和视网膜。从受体功能和治疗潜力的角度来看，δ 型阿片受体（DOR）是一个非常有吸引力的靶点。由于在小鼠诱变方面的快速进展以及小分子作为 DOR 激动剂的开发，近年来 DOR 出现了新的功能和作用。本文综述了 DOR 激动剂在一般神经保护，特别是视网膜神经保护中的最新进展。本文重点介绍了 DOR 功能在神经保护方面的选定研究，而不是详尽无遗，目的是突出 DOR 功能的研究。我们还强调了我们使用啮齿动物模型进行的临床前研究，以证明 DOR 激动剂对视网膜神经保护的潜力。基于现有的文献和我们最近发表的关于眼睛的研究数据，DOR 激动剂具有治疗能力，可以保护视网膜和视神经免受青光眼及其他可能的视网膜病变的损伤。本文还强调了与 DOR 相关的神经保护信号事件。需要对 DOR 进行转化研究，以认识到它们在临床应用中的潜力，如在青光眼治疗中的应用。
