RESEARCH ON PATHOGENESIS AND TREATMENT OF OCULAR VASCULAR DISEASES

眼血管疾病发病机制及治疗研究

• 批准号: 09307040
• 负责人: INOMATA Hajime
• 金额: $ 22.27万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09307040/
• 关键词: Neovascularization; Malignant Melanoma; Adenovirus Vector; Subretinal Neovascularization; Wound Healing; Tissue Plasminogen Activator; Transforming Growth Factor-β; Vascular Endothelial Growth Factor; トランスフォーミング増殖因子TGF-b; 糖尿病網膜症; 遺伝子治療; 組織因子

We examined the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma, and it was found that the VEGF receptor (flt-1) gene inhibited the growth of the tumor. However, it caused the severe skin ulcer. Similarly, experimental subretinal neovascularization was inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection : as a role of VEGF and possible treatment for SRN in age-related macular degeneration. However, severe damages occurred in the sensory retina.From these experimental studies, it became clear that neovascularization is rather important and indispensable phenomenon for wound healing of the tissues and organs. Therefore, it seems to be more important to inhibit the inflammation and/or tissue fibrosis during the wound healing.To have the ideal wound healing, we prepared adenovirus vector to inhibit tissue plasminogen activator and transforming growth factor-β (TGF-β). Our results demonstrated that TGF-β indeed plays a critical role in the process of corneal opacification, edema and angiogenesis, and that adenovirus-mediated expression of a soluble TGF-β receptor can be therapeutically useful.

我们检查了腺病毒介导的基因转移血管内皮生长因子（VEGF）对实验性眼睑恶性黑色素瘤生长的影响，发现VEGF受体（FLT-1）基因抑制了肿瘤的生长。但是，它导致严重的皮肤溃疡。同样，通过腺病毒介导的固体VEGF/FLT-1受体基因转移抑制了视网膜下新血管形成：作为VEGF的作用和SRN在与年龄相关的黄斑变性中的作用。然而，在感觉视网膜中发生了严重的损害。从这些实验研究中，很明显，对于组织和器官的伤口愈合，新血管化是相当重要的，不可或缺的现象。因此，在伤口愈合过程中抑制感染和/或组织纤维化似乎更为重要。为了进行理想的伤口愈合，我们准备了腺病毒载体来抑制组织纤溶酶原激活剂并转化生长因子-β（TGF-β）。我们的结果表明，TGF-β确实在角膜无关，水肿和血管生成过程中起着至关重要的作用，并且腺病毒介导的可溶性TGF-β受体的表达可以在治疗上有用。

项目成果

Oshima Y: "Synergistic effect of electric pulses and bleomycin on cultured rabbit subconjunctival fibroblasts." Graefe's Arch Clin Exp Ophthalmol. 236・1. 52-60 (1998)

Oshima Y：“电脉冲和博来霉素对培养的兔结膜下成纤维细胞的协同作用。”Graefes Arch Clin Exp Ophthalmol。

石橋 達朗: "糖尿病網膜症-病理学-" 日本臨床. 55・増刊. 948-952 (1997)

Tatsuro Ishibashi：“糖尿病视网膜病变-病理学”，日本临床杂志 55/特刊 948-952（1997 年）。

Inomata H, et al: "Depigmented atrophic lesions in sunset glow fundi in Vogt-Koyanagi-Harada disease."Am J Ophthalmol. 130・4(印刷中). (2001)

Inomata H 等人：“Vogt-Koyanagi-Harada 病中的日落色素萎缩性病变”，Am J Ophamol，2001 年。

猪俣 孟: "黄斑部の名称" 日本眼科学会雑誌. 101・3. 201-208 (1997)

猪俣孟：《黄斑部的名称》日本眼科学会杂志101・3（1997）。

猪俣 孟: "糖尿病眼科の臨床" 福田 雅俊,松井 瑞夫,猪俣 孟, 188 (1997)

孟猪又：《临床糖尿病眼科学》Masatoshi Fukuda、Mizuo Matsui、Meng Inomata，188（1997）