Department of Human Science and Promotion of Quality of Life, San Raffaele Open University of Rome, Italy; Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Peptides. 2017 Nov;97:64-69. doi: 10.1016/j.peptides.2017.09.014. Epub 2017 Sep 28.
Diabetic retinopathy (DR) is a microvascular complication of diabetes. Hyperglycemic/hypoxic microenvironment concurs to aberrant angiogenesis characterizing the pathology and activates many downstream target genes including inflammatory cytokines and vasoactive peptides, such as interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF). It has been largely demonstrated that pituitary adenylate cyclase-activating peptide (PACAP) plays a protective effect in DR. In the present study, we investigated the role of PACAP to protect retinal tissue through IL-1β and VEGF expression. Diabetes was induced in rats by streptozotocin (STZ) injection, and one week later a single intravitreal injection of 100μM PACAP was administrated. Analyses of IL-1β and VEGF levels were performed three weeks after diabetes induction. The results demonstrated that a single intraocular administration of PACAP significantly reduced the expression of IL-1β in diabetic animals. Moreover, it affects VEGF and its receptors (VEGFRs) levels and interferes with their retinal layers distribution as showed by confocal microscopy analysis. In particular, PACAP treatment downregulates VEGF and VEGFRs that are increasingly expressed in STZ-treated animals as compared to controls. These results indicate that PACAP plays an important role to attenuate the early phase of DR.
糖尿病性视网膜病变（DR）是糖尿病的一种微血管并发症。高血糖/缺氧微环境促使病理特征发生异常血管生成，并激活许多下游靶基因，包括炎症细胞因子和血管活性肽，如白细胞介素-1β（IL-1β）和血管内皮生长因子（VEGF）。大量研究表明，垂体腺苷酸环化酶激活肽（PACAP）在 DR 中发挥保护作用。在本研究中，我们通过 IL-1β 和 VEGF 的表达来研究 PACAP 保护视网膜组织的作用。通过链脲佐菌素（STZ）注射诱导大鼠糖尿病，一周后单次玻璃体内注射 100μM PACAP。在诱导糖尿病 3 周后进行 IL-1β 和 VEGF 水平分析。结果表明，单次眼内给予 PACAP 可显著降低糖尿病动物中 IL-1β 的表达。此外，它还影响 VEGF 及其受体（VEGFRs）的水平，并通过共聚焦显微镜分析干扰其在视网膜层中的分布。特别是，PACAP 治疗可下调在 STZ 处理动物中与对照组相比表达增加的 VEGF 和 VEGFRs。这些结果表明，PACAP 在减轻 DR 的早期阶段发挥重要作用。
