Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129.08035, Barcelona, Spain.
Endocrine. 2014 Jun;46(2):209-14. doi: 10.1007/s12020-014-0232-z. Epub 2014 Mar 14.
Somatostatin (SST) is abundantly produced by the human retina, and the main source is the retinal pigment epithelium (RPE). SST exerts relevant functions in the retina (neuromodulation, angiostatic, and anti-permeability actions) by interacting with SST receptors (SSTR) that are also expressed in the retina. In the diabetic retina, a downregulation of SST production does exist. In this article, we give an overview of the mechanisms by which this deficit of SST participates in the main pathogenic mechanisms involved in diabetic retinopathy (DR): neurodegeneration, neovascularization, and vascular leakage. In view of the relevant SST functions in the retina and the reduction of SST production in the diabetic eye, SST replacement has been proposed as a new target for treatment of DR. This could be implemented by intravitreous injections of SST analogs or gene therapy, but this is an aggressive route for the early stages of DR. Since topical administration of SST has been effective in preventing retinal neurodegeneration in STZ-induced diabetic rats, it seems reasonable to test this new approach in humans. In this regard, the results of the ongoing clinical trial EUROCONDOR will provide useful information. In conclusion, SST is a natural neuroprotective and antiangiogenic factor synthesized by the retina which is downregulated in the diabetic eye and, therefore, its replacement seems a rational approach for treating DR. However, clinical trials will be needed to establish the exact position of targeting SST in the treatment of this disabling complication of diabetes.
生长抑素（SST）在人视网膜中大量产生，其主要来源是视网膜色素上皮（RPE）。SST 通过与也在视网膜中表达的 SST 受体（SSTR）相互作用，在视网膜中发挥相关功能（神经调节、血管生成抑制和抗通透性作用）。在糖尿病视网膜中，确实存在 SST 产生的下调。在本文中，我们概述了这种 SST 缺乏参与糖尿病性视网膜病变（DR）主要发病机制的机制：神经退行性变、新生血管形成和血管渗漏。鉴于 SST 在视网膜中的相关功能以及糖尿病眼中 SST 产生的减少，已经提出 SST 替代作为治疗 DR 的新靶点。这可以通过玻璃体内注射 SST 类似物或基因治疗来实现，但对于 DR 的早期阶段，这是一种激进的方法。由于 SST 的局部给药已被证明可有效预防 STZ 诱导的糖尿病大鼠的视网膜神经退行性变，因此在人类中测试这种新方法似乎是合理的。在这方面，正在进行的临床试验 EUROCONDOR 的结果将提供有用的信息。总之，SST 是一种由视网膜合成的天然神经保护和抗血管生成因子，在糖尿病眼中下调，因此其替代似乎是治疗 DR 的合理方法。然而，需要进行临床试验来确定在治疗这种糖尿病致残并发症时靶向 SST 的确切位置。
