Fouda Abdelrahman Y, Eldahshan Wael, Narayanan S Priya, Caldwell R William, Caldwell Ruth B
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Front Pharmacol. 2020 Mar 17;11:277. doi: 10.3389/fphar.2020.00277. eCollection 2020.
Ischemic retinopathies represent a major cause of visual impairment and blindness. They include diabetic retinopathy (DR), acute glaucoma, retinopathy of prematurity (ROP), and central (or branch) retinal artery occlusion (CRAO). These conditions share in common a period of ischemia or reduced blood supply to the retinal tissue that eventually leads to neuronal degeneration. Similarly, acute brain injury from ischemia or trauma leads to neurodegeneration and can have devastating consequences in patients with stroke or traumatic brain injury (TBI). In all of these conditions, current treatment strategies are limited by their lack of effectiveness, adverse effects or short time window for administration. Therefore, there is a great need to identify new therapies for acute central nervous system (CNS) injury. In this brief review article, we focus on the pathway of the arginase enzyme as a novel therapeutic target for acute CNS injury. We review the recent work on the role of arginase enzyme and its downstream components in neuroprotection in both retina and brain acute injury models. Delineating the similarities and differences between the role of arginase in the retina and brain neurodegeneration will allow for better understanding of the role of arginase in CNS disorders. This will also facilitate repurposing the arginase pathway as a new therapeutic target in both retina and brain diseases.
缺血性视网膜病变是视力损害和失明的主要原因。它们包括糖尿病视网膜病变(DR)、急性青光眼、早产儿视网膜病变(ROP)以及视网膜中央(或分支)动脉阻塞(CRAO)。这些病症的共同之处在于存在一段视网膜组织缺血或血液供应减少的时期,最终导致神经元变性。同样,缺血或创伤引起的急性脑损伤会导致神经变性,并且在中风或创伤性脑损伤(TBI)患者中可能产生毁灭性后果。在所有这些病症中,目前的治疗策略都因其有效性不足、副作用或给药时间窗短而受到限制。因此,迫切需要确定针对急性中枢神经系统(CNS)损伤的新疗法。在这篇简短的综述文章中,我们重点关注精氨酸酶途径作为急性CNS损伤的新型治疗靶点。我们回顾了近期关于精氨酸酶及其下游成分在视网膜和脑急性损伤模型的神经保护作用的研究。阐明精氨酸酶在视网膜和脑神经元变性中的作用异同,将有助于更好地理解精氨酸酶在中枢神经系统疾病中的作用。这也将促进将精氨酸酶途径重新用作视网膜和脑疾病的新治疗靶点。