Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity.

Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity.
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DOI:
10.1096/fj.11-184127
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发表时间:
2012-02
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
通讯作者:
D'Amore PA
D'Amore PA
中科院分区:
其他
文献类型:
--
作者:
Sekiyama E;Saint-Geniez M;Yoneda K;Hisatomi T;Nakao S;Walshe TE;Maruyama K;Hafezi-Moghadam A;Miller JW;Kinoshita S;D'Amore PA

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年龄相关性黄斑变性(AMD)是西方世界致盲的主要原因。在晚期AMD中,来自绒毛膜毛细血管(CC)的新血管侵入布鲁氏膜(Bruch’s membrane, BrM)进入视网膜,形成脉络膜新生血管(choroidal nevascular, CNV)。BrM是一种位于视网膜色素上皮(RPE)和CC之间的弹性层,被认为是抵抗CNV的物理和功能屏障。早期AMD患者的BrM以抗血管生成因子水平降低为特征,包括内皮抑素、血小板反应蛋白-1 (TSP-1)和色素上皮衍生因子(PEDF),以及弹性层变性。根据之前的一篇报道,热量会增加人体皮肤中弹性蛋白的表达,我们研究了热量对人体ARPE-19细胞生成BrM成分的影响。热处理刺激了BrM成分的产生,包括体外培养的TSP-1、PEDF和对流层弹性蛋白,并增加了小鼠角膜袋试验中RPE的抗血管生成活性。采用红外二极管激光对视网膜进行热预处理,观察热对视网膜新生细胞形成的影响。热处理在体内阻断了实验性CNV的发展。这些发现表明,热处理可以恢复BrM的完整性和防止新血管生长的屏障功能。-Sekiyama, E., Saint-Geniez, M., Yoneda, K., Hisatomi, T., Nakao, S., Walshe, T. E., Maruyama, K., Hafezi-Moghadam, A., Miller, J. W., Kinoshita, S., D'Amore, P. A.热处理视网膜色素上皮诱导弹性层成分的产生和抗血管生成活性。
Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV. The BrM of patients with early AMD are characterized by decreased levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithelium-derived factor (PEDF), as well as by degeneration of the elastic layer. Motivated by a previous report that heat increases elastin expression in human skin, we examined the effect of heat on human ARPE-19 cell production of BrM components. Heat treatment stimulated the production of BrM components, including TSP-1, PEDF, and tropoelastin in vitro and increased the antiangiogenic activity of RPE measured in a mouse corneal pocket assay. The effect of heat on experimental CNV was investigated by pretreating the retina with heat via infrared diode laser prior to the induction of CNV. Heat treatment blocked the development of experimental CNV in vivo. These findings suggest that heat treatment may restore BrM integrity and barrier function against new vessel growth.—Sekiyama, E., Saint-Geniez, M., Yoneda, K., Hisatomi, T., Nakao, S., Walshe, T. E., Maruyama, K., Hafezi-Moghadam, A., Miller, J. W., Kinoshita, S., D'Amore, P. A. Heat treatment of retinal pigment epithelium induces production of elastic lamina components and anti-angiogenic activity.
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