TGF-β和BMP在原发性开角型青光眼中的作用

Role of TGF-beta and BMP in Primary Open-angle Glaucoma

眼压升高是原发性开角型青光眼（primary open-angle glaucoma , POAG）发生和发展最主要的危险因素,是由小梁网途径的房水外流排出系统发生病变、房水流出阻力增加所致。 POAG 患者小梁网结构最显著的改变是小梁网近小管组织的纤维细胞外基质增多。现表明小梁网细胞外基质的数量和质量的变化是由多种信号通路相互作用调控其合成和降解的结果。来源于房水的转化生长因子-β1（transforming growth factor-β1, TGF-β1）和转化生长因子-β2（transforming growth factor-β2, TGF-β2）可局部诱导小梁网细胞表达多种细胞外基质。骨形态发生蛋白-7（bone morphogenetic protein-7, BMP-7）和骨形态发生蛋白-4（bone morphogenetic protein-4, BMP-4）可有效地拮抗 TGF-β诱导的细胞外基质沉积。这种拮抗作用是通过 Smad7介导的。 Smad7是抑制 TGF-β2信号的一个关键分子。

Elevated intraocular pressure （IOP） is the most critical risk factor for primary open angle glaucoma （POAG） . It results from an abnormally high aqueous humor outflow resistance in the juxtacanalicular region of the trabecular meshwork. A distinct structural change in the trabecular meshwork of patients with POAG is the increase in fibrillar extracellular matrix in the juxtacanalicu-lar region of the trabecular meshwork. Recently, research shows that the quality and quantity of the extracellular matrix in the trabecular meshwork are regulated by several signaling molecules that in-teract with each other to promote the synthesis, degradation, or modification of extracellular matrix. Transforming growth factor-β1 and β2 （TGF-β1 and TGF-β2） which derive from the aqueous humor may locally induce the expression of a variety of extracellular matrix molecules in trabecular mesh-work cells. Bone morphogenetic proteins （BMP） -7 and -4 can effectively antagonize the effects of TGF-β on extracellular matrix deposition. The antagonizing effects of BMP-7 are mediated in trabec-ular meshwork cells through Smad7, which is a key molecule to inhibit TGF-β2 signaling in the tra-becular meshwork.