CEDOC - Chronic Diseases Research Center, NOVA Medical School, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056, Lisboa, Portugal; Bioengineering- Cell Therapies and Regenerative Medicine PhD Program, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.
CEDOC - Chronic Diseases Research Center, NOVA Medical School, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056, Lisboa, Portugal.
Exp Eye Res. 2020 May;194:108027. doi: 10.1016/j.exer.2020.108027. Epub 2020 Apr 4.
Diabetic retinopathy (DR) is considered as a diabetes-related complication that can lead to severe visual impairments. By 2030, it is expected that 1 in 5 adults will suffer from the disease. Suitable animal models for chronic DR are essential for a better understanding of the pathophysiology and to further develop new treatments. The Ins2 mouse is a type 1 diabetes model that shows signs of both early and late stages of DR, including pericyte loss, increased vascular permeability, increased acellular capillaries and neovascularization. To further characterize DR in the Ins2 mouse model, we have evaluated the protein levels of the angiogenesis inducers vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and the angiogenesis inhibitor pigment epithelium-derived factor (PEDF). Additionally, we have analyzed the protein expression profile of the glial markers ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) as well as of the chemokine monocyte chemoattractant protein 1 (MCP-1). In this study we demonstrate that, with disease progression, there is the development of an inflammatory response and an unbalanced expression of pro- and antiangiogenic factors in the neural retina and in the retinal pigment epithelium (RPE) of Ins2 mice. Therefore, our data provide support for the diabetic retinopathy features detected in the Ins2 retina, reflecting what is observed in the human pathology.
糖尿病视网膜病变（DR）被认为是一种与糖尿病相关的并发症，可导致严重的视力损害。到 2030 年，预计每 5 个成年人中就有 1 个会患上这种疾病。合适的慢性 DR 动物模型对于更好地理解其病理生理学以及进一步开发新的治疗方法至关重要。Ins2 小鼠是一种 1 型糖尿病模型，它表现出 DR 的早期和晚期阶段的特征，包括周细胞丧失、血管通透性增加、无细胞毛细血管增加和新生血管形成。为了进一步表征 Ins2 小鼠模型中的 DR，我们评估了血管生成诱导因子血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）以及血管生成抑制剂色素上皮衍生因子（PEDF）的蛋白水平。此外，我们还分析了神经视网膜和 Ins2 小鼠视网膜色素上皮（RPE）中神经胶质标志物离子钙结合衔接分子 1（Iba1）和神经胶质纤维酸性蛋白（GFAP）以及趋化因子单核细胞趋化蛋白 1（MCP-1）的蛋白表达谱。在这项研究中，我们证明随着疾病的进展，Ins2 小鼠的神经视网膜和 RPE 中会出现炎症反应和促血管生成因子与抗血管生成因子的表达失衡。因此，我们的数据为 Ins2 视网膜中检测到的糖尿病视网膜病变特征提供了支持，反映了在人类病理学中观察到的情况。
