Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes.
Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes.
复制标题
生长抑素的局部给药可防止实验性糖尿病中的视网膜神经退行性。
作者：
Hernández C;García-Ramírez M;Corraliza L;Fernández-Carneado J;Farrera-Sinfreu J;Ponsati B;González-Rodríguez A;Valverde AM;Simó R
视网膜神经变性是糖尿病视网膜病变（DR）发病机制中的早期事件。生长抑素（SST）是一种内源性神经保护肽，在糖尿病眼下调。该研究的目的是测试SST局部给药在预防视网膜神经变性中的有用性。为此目的，用SST滴眼液或溶剂处理链脲佐菌素诱导的糖尿病（STZ-DM）大鼠15天。用溶剂处理的非糖尿病大鼠作为对照组。通过视网膜电图（ERG）评估功能异常，并通过测量胶质细胞活化和细胞凋亡率评估神经退行性变。此外，还检查了促凋亡（FasL、Bid和caspase-8和caspase-3的活化）和存活信号通路（BclxL）。还测定了谷氨酸及其主要转运体谷氨酸/天冬氨酸转运体（GLAST）的视网膜内浓度。SST滴眼液治疗可预防STZ-DM大鼠的ERG异常、神经胶质活化、细胞凋亡以及促凋亡信号和存活信号之间的失衡。此外，SST滴眼液抑制视网膜中谷氨酸的积累和糖尿病诱导的GLAST下调。我们的结论是，局部施用SST在预防糖尿病引起的视网膜神经变性方面具有有效作用。此外，我们的研究结果开辟了一个新的预防药理学策略，针对早期阶段的DR。
Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Somatostatin (SST) is an endogenous neuroprotective peptide that is downregulated in the diabetic eye. The aim of the study was to test the usefulness of topical administration of SST in preventing retinal neurodegeneration. For this purpose, rats with streptozotocin-induced diabetes mellitus (STZ-DM) were treated with either SST eye drops or vehicle for 15 days. Nondiabetic rats treated with vehicle served as a control group. Functional abnormalities were assessed by electroretinography (ERG), and neurodegeneration was assessed by measuring glial activation and the apoptotic rate. In addition, proapoptotic (FasL, Bid, and activation of caspase-8 and caspase-3) and survival signaling pathways (BclxL) were examined. Intraretinal concentrations of glutamate and its main transporter glutamate/aspartate transporter (GLAST) were also determined. Treatment with SST eye drops prevented ERG abnormalities, glial activation, apoptosis, and the misbalance between proapoptotic and survival signaling detected in STZ-DM rats. In addition, SST eye drops inhibited glutamate accumulation in the retina and GLAST downregulation induced by diabetes mellitus. We conclude that topical administration of SST has a potent effect in preventing retinal neurodegeneration induced by diabetes mellitus. In addition, our findings open up a new preventive pharmacological strategy targeted to early stages of DR.
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