The investigation into an intreretinal pathology and a molecular biological mechanism of diabetic retinopathy

糖尿病视网膜病变的视网膜内病理学和分子生物学机制的研究

• 批准号: 13307049
• 负责人: HONDA Yoshihito
• 金额: $ 27.12万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13307049/
• 关键词: LDL-receptor; ob; ob mouse; leptin; stetin; angiotensin; ATI receptor; diabetic retinopathy; VEGF; レニン-アンジオテンシン系; LOLレセプター; Ang2; AT1ノックアウトマウス; レニン・アンジオテンシン系; 網膜血管増殖

Vascular endothelial growth factor (VEGF) mediates such ischemia-induced ocular neovascularization as diabetic retinopathy and age-related macular degeneration. In this research, we investigated the molecular mechanism how VEGF is highly expressed in retinas of diabetic retinopathy. Lectin-like oxidized LDL receptor 1(LOX1) is assume to play an important role in VEGF hyperexpression. We reveal a role for LOX1 in cell adhesion in endotoxin-induced inflammation. (PNAS2003 ; 4 ; 100 ; 3 ; 1274-9) Statin inhibits leucocyte-endothelial interaction and prevents neuroral death induced by ischemia-reperfusion injury in the rat retina, so statin has potential of therapeutic drug in diabetic retinopathy. (Arch Ophthal 2002 ; 120 ; 12 ; 1707-13). Leptin is known to be highly concentrated in blood and vitreous of diabetic patients. Leptin has angiogenic effect and we revealed that in ob/ob mice vascular proliferation is inhibited, and VEGF expression is inhibited. (in press) We revealed angiotensin potentiates the expression of VEGF receptor and angiopoietin 2. (Diabetes 2001 ; 50 ; 867-875) These effects are mediated by angiotensin type 1 receptor. These reveals a possibility that the control of molecular mechanism in LDL receptor, leptin, and angiotensin2 leads to inhibition of early change in diabetic retinopathy.

血管内皮生长因子（VEGF）介导缺血诱导的眼部新生血管形成，如糖尿病视网膜病变和年龄相关性黄斑变性。本研究旨在探讨VEGF在糖尿病视网膜病变中高表达的分子机制。凝集素样氧化型低密度脂蛋白受体1（LOX 1）被认为在VEGF高表达中起重要作用。我们揭示了LOX 1在内毒素诱导的炎症中细胞粘附中的作用。（PNAS 2003; 4个; 100人; 3个; 1274-9）他汀类药物抑制白细胞-内皮细胞相互作用，预防大鼠视网膜缺血再灌注损伤诱导的神经元死亡，因此他汀类药物具有成为糖尿病视网膜病变治疗药物的潜力。(Arch Ophthal 2002 ; 120 ; 12 ; 1707-13）。已知瘦素在糖尿病患者的血液和玻璃体中高度浓缩。瘦素具有血管生成作用，我们发现在ob/ob小鼠中血管增殖受到抑制，并且VEGF表达受到抑制。(in我们发现血管紧张素增强VEGF受体和血管生成素2的表达。（Diabetes 2001 ; 50 ; 867-875）这些作用由血管紧张素1型受体介导。这些揭示了LDL受体、瘦素和血管紧张素2的分子机制的控制导致糖尿病视网膜病变的早期变化的抑制的可能性。

项目成果

Miyamoto M, Manaki M, Takagi H, Suzuma I, Suzuna S, Honda Y: "Contrasting Effect of Estrogen on VEGF Induction under Different Oxygen Status and Its Role in Murine Retinopathy of Prematuity"Invest Ophthalmol Vis Sci. (in press).

Miyamoto M、Manaki M、Takagi H、Suzuma I、Suzuna S、Honda Y：“不同氧状态下雌激素对 VEGF 诱导的对比作用及其在小鼠早产儿视网膜病变中的作用”Invest Ophasemol Vis Sci。

Yamoshiro K, et al.: "Suppressive effects of selectin inhibitor SKK-60060 on the leucocyte infiltration during endotoxin induced uveitis"Br J Ophthalmol.. 57(4). 476-480 (2003)

Yamoshiro K 等人：“选择素抑制剂 SKK-60060 对内毒素诱导的葡萄膜炎期间白细胞浸润的抑制作用”Br J Ophthalmol.. 57(4)。

Takagi H, Suzuma K, Otani A, Oh H, Koyama S, Ohashi H, Honda Y: "Role of Vitronectin Receptor-Type Integrins and Osteopontin in Ischemia-Induced Retinal NeovascuIarization"Jpn J Ophthalmol. (in press).

Takagi H、Suzuma K、Otani A、Oh H、Koyama S、Ohashi H、Honda Y：“玻连蛋白受体型整联蛋白和骨桥蛋白在缺血引起的视网膜新生血管化中的作用”Jpn J Ophasemol。

Yamashiro K, et al.: "Suppressive effects of selectin inhibitor SKK-60060 on the leucocyte infiltration during endotoxin induced uveitis"Br J Ophthalmol. 87(4). 476-480 (2003)

Yamashiro K 等人：“选择素抑制剂 SKK-60060 对内毒素诱导的葡萄膜炎期间白细胞浸润的抑制作用”Br J Ophamol。

Honjo M, et al.: "Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation"Proe Natl Aead Sci USA. 100(3). 1274-1279 (2003)

Honjo M 等人：“凝集素样氧化 LDL 受体 1 是参与内毒素诱导炎症的细胞粘附分子”Proe Natl Aead Sci USA。