New strategy to treat diabetic retinopathy using stabilization of hyalocyte-vasucular endothelial cell correlation

利用稳定透明细胞-血管内皮细胞相关性治疗糖尿病视网膜病变的新策略

• 批准号: 21592215
• 负责人: YAMASHITA Hidetoshi
• 金额: $ 2.91万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592215/
• 关键词: 糖尿病黄斑浮腫; 網膜内境界膜; 硝子体細胞; グリア細胞; 網膜ー硝子体界面; 血管内皮細胞; ステロイド; 点眼約治療; 炎症性サイトカイン; ヒアルロン酸; ステロイド点眼; 非観血的治療; 点眼治療; 眼内移行; 網膜-硝子体界面; 網膜-硝子体海面

Ocular angiogenesis is regulated by polypeptides including cytokines, which are known to affect vascular endothelial cells. We have investigated that hyalocytes interact with vascular endothelial cells, and some cytokines affect these interactions. To determine the effect of various chemically active agents on the viability of endothelial cells alone and cocultured with hyalocytes. The viability of human retinal endothelial cells (HREC_s) was determined after exposure to IL-1α, IL-1β, IL-6, TNFα and VEGF using the MTT assay. These results were compared to the viability when the HRECs were cocultured with porcine hyalocytes that had been exposed to different types of cytokines. The effects of bevacizumab, fenofibrate and dexamethasone on the viability of HRECs in coculture with hyalocytes were also assessed. Ten micrograms/millilitre of bevacizumab decreased the percentage of living HRECs stimulated by VEGF without hyalocytes, but with the hyalocytes, 100 μg/ml of bevacizumab was requir … More ed to decrease the percentage of viable HRECs stimulated by VEGF. Dexamethasone at 50 μg/ml, decreased the viability of HRECs stimulated by IL-1α, IL-1β, IL-6 and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured. Coculturing HRECs with vitreous-derived hyalocytes depressed the effects of cytokines, bevacizumab, fenofibrate and dexamethasone. This suggests that the vitreal hyalocytes may play a role in pathogenic endothelial cell proliferation in vivo. In addition, inflammatory processes play important roles in diabetic retinopathy and maculopathy involving hyalocytes and endothelial cells.Upon the above results, we examined the effects of steroid eye drops to treat diabetic maculopathy. We evaluated the efficacy of treatment refractory diabetic macular edema (DME) after vitrectomy with difluprednate ophthalmic emulsion 0.05% (DurezolR). This study enrolled patients with refractory diabetic macular edema in our clinic. In all subjects, more than 3 months had passed since any prior treatments. The subject eyes were treated with Durezol^(R) 4 times daily for the first month, and then twice daily for 2 months (eye drop group). The mean retinal thickness was improved significantly. Instillation of difluprednate ophthalmic emulsion 0.05% is a safe and effective treatment modality that does not require surgical intervention and does not produce severe side effects. Less

眼部血管生成受包括细胞因子的多肽调节，已知其影响血管内皮细胞。我们已经研究了透明细胞与血管内皮细胞的相互作用，一些细胞因子影响这些相互作用。确定各种化学活性剂对单独内皮细胞和与透明细胞共培养的内皮细胞活力的影响。采用MTT法检测IL-1α、IL-1β、IL-6、TNFα和VEGF对人视网膜内皮细胞（HREC_s）活性的影响。将这些结果与HREC与暴露于不同类型细胞因子的猪透明细胞共培养时的活力进行比较。还评估了贝伐单抗、非诺贝特和地塞米松对与透明细胞共培养的HREC活力的影响。10 μ g/ml的贝伐单抗可降低VEGF刺激的不含透明细胞的HREC的存活率，但含透明细胞的HREC需要100 μg/ml的贝伐单抗。 ...更多信息 艾德降低VEGF刺激的活HREC的百分比。50 μg/ml地塞米松可降低IL-1α、IL-1β、IL-6和VEGF刺激的无透明细胞的HRECs的活力，但不能降低共培养的HRECs的活力。HREC与玻璃体来源的透明细胞共培养抑制了细胞因子、贝伐单抗、非诺贝特和地塞米松的作用。提示玻璃体透明细胞可能在体内致病性内皮细胞增殖中起作用。此外，炎症过程在糖尿病视网膜病变和涉及透明细胞和内皮细胞的黄斑病变中起重要作用。根据上述结果，我们检查了类固醇滴眼液治疗糖尿病黄斑病变的效果。我们评价了0.05%二氟泼尼酯眼用乳剂（DurezolR）治疗玻璃体切除术后难治性糖尿病性黄斑水肿（DME）的疗效。本研究招募了我们诊所的难治性糖尿病黄斑水肿患者。在所有受试者中，自任何既往治疗以来已超过3个月。受试者的眼睛用Durezol^（R）治疗，第一个月每天4次，然后每天2次，持续2个月（滴眼剂组）。平均视网膜厚度明显改善。滴注0.05%二氟泼尼酯眼用乳剂是一种安全有效的治疗方式，不需要手术干预，也不会产生严重的副作用。少

项目成果

シンポジウム「糖尿病黄斑浮腫の薬物治療-新たな可能性と問題点」ステロイド眼局所治療の展望

研讨会“糖尿病黄斑水肿的药物治疗——新的可能性和问题”局部类固醇治疗的前景

• 发表时间: 2011
• 作者: 加治優一;Oshika T;Okamoto F;藤井紀子;後藤早紀子
• 通讯作者: 後藤早紀子

糖尿病黄斑浮腫における網膜-硝子体界面病態の3次元的画像観察

糖尿病黄斑水肿视网膜玻璃体界面病理的三维图像观察

• 发表时间: 2009
• 作者: 阿部さち;山本禎子;中野早紀子;桐井枝里子;柏木佳子;山下英俊
• 通讯作者: 山下英俊

糖尿病黄斑浮腫に対するステロイド点眼治療の長期経過

类固醇滴眼液治疗糖尿病黄斑水肿的长期疗程

• 发表时间: 2010
• 作者: 後藤早紀子;山本禎子;桐井枝里子;阿部さち;山下英俊
• 通讯作者: 山下英俊

糖尿病 最新の治療,2010-2012

2010-2012年糖尿病最新治疗方法

• 发表时间: 2010
• 作者: 山本昌弘、(3番目;他5名);Kanazawa I;Kanazawa I;山本昌弘;林公美;金沢一平;金沢一平;高岡伸;Yamamoto M;Yamamoto M;山本昌弘;Yamamoto M;Yamaguchi T;山本昌弘;山口徹;林公美;矢野彰三;金沢一平;Yamamoto M;Yamaguchi T;Yamaguchi T;Yamamoto M;Yamaguchi T;山本昌弘;Yamamoto M;Yamaguchi T;Yamaguchi T;金沢一平;金沢一平;山本昌弘;山本昌弘;金沢一平;山本昌弘;金沢一平;金沢一平;山本昌弘;山本昌弘;山本昌弘;山本昌弘
• 通讯作者: 山本昌弘

糖尿病網膜症の治療戦略

糖尿病视网膜病变的治疗策略

• 发表时间: 2011
• 期刊: 臨床眼科
• 作者: 山下英俊;山本禎子;川崎良;佐藤浩章;佐藤さくら;斉藤公子;後藤早紀子;望月典子;田邉祐資;桐井枝里子;阿部さち;本間慶;嘉山孝正
• 通讯作者: 嘉山孝正