Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy
Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy
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DOI：
10.1007/s00592-016-0895-4
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发表时间：
2016-12-01
影响因子：
3.8
通讯作者：
Porta, Massimo
中科院分区：
文献类型：
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作者：
Beltramo, Elena;Lopatina, Tatiana;Porta, Massimo
糖尿病视网膜病变被认为是一种微血管疾病，但最近的证据强调了早期参与微血管和神经改变之间的相互作用的神经视网膜。局部施用生长抑素（SST），一种具有抗血管生成特性的神经保护分子，可预防糖尿病诱导的动物视网膜神经变性。α 2肾上腺素能受体激动剂溴莫尼定（BRM）可降低糖尿病大鼠玻璃体视网膜血管内皮生长因子，抑制血视网膜屏障的破坏。然而，SST和BRM对微血管细胞的影响尚未研究。方法检测人视网膜周细胞（HRP）表面SST受体1-5的表达。我们随后评估了有/无SST/BRM的糖尿病样条件（高糖和/或缺氧）对HRP存活的影响。将内皮细胞（EC）和光感受器维持在上述条件下，并将其条件培养基（CM）用于培养HRP。反之亦然，HRP-CM用于EC和光感受器。结果HRP表达SST受体1（SSTR 1）。模拟糖尿病受试者中发生的葡萄糖波动比稳定的高葡萄糖和缺氧条件对周细胞和光感受器的损害更大。SST/BRM加入HRP在糖尿病样条件下减少EC凋亡。然而，无论是SST还是BRM改变的反应，周细胞和神经视网膜血管crosstalk在糖尿病样conditions.Conclusions视网膜周细胞表达SSTR 1，表明他们可以是一个目标SST。暴露于SST/BRM没有直接或通过神经视网膜介导的不良反应，表明这些分子可以安全地用于眼部疾病的治疗。
Aims Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The alpha(2)-adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats. However, SST and BRM effects on microvascular cells have not yet been studied. We investigated the behaviour of these drugs on the crosstalk between microvasculature and neuroretina.Methods Expression of SST receptors 1-5 in human retinal pericytes (HRP) was checked. We subsequently evaluated the effects of diabetic-like conditions (high glucose and/or hypoxia) with/without SST/BRM on HRP survival. Endothelial cells (EC) and photoreceptors were maintained in the above conditions and their conditioned media (CM) used to culture HRP. Vice versa, HRP-CM was used on EC and photoreceptors. Survival parameters were assessed.Results HRP express the SST receptor 1 (SSTR1). Glucose fluctuations mimicking those occurring in diabetic subjects are more damaging for pericytes and photoreceptors than stable high glucose and hypoxic conditions. SST/BRM added to HRP in diabetic-like conditions decrease EC apoptosis. However, neither SST nor BRM changed the response of pericytes and neuroretina-vascular crosstalk under diabetic-like conditions.Conclusions Retinal pericytes express SSTR1, indicating that they can be a target for SST. Exposure to SST/BRM had no adverse effects, direct or mediated by the neuroretina, suggesting that these molecules could be safely evaluated for the treatment of ocular diseases.