Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target.
Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target.
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DOI：
10.1038/srep24453
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发表时间：
2016-04-14
影响因子：
4.6
通讯作者：
Wormstone IM
中科院分区：
文献类型：
--
作者：
Eldred JA;McDonald M;Wilkes HS;Spalton DJ;Wormstone IM
白内障手术后，由于伤口愈合反应，即后囊膜混浊（PCO），数百万患者发生继发性视力丧失。在白内障摘除后，人工晶状体（IOL）被植入残留的晶状体组织，即囊袋。标准iol允许前囊和后囊物理连接。这对人工晶状体施加压力，并改善其与下层后囊的接触。新的开袋式人工晶状体设计分离了前囊和后囊，进一步降低了PCO的发生率。据推测，这是由于细胞因子可用性降低，由于更大的冲洗袋。因此，我们利用人晶状体细胞和组织培养模型探讨生长因子限制对后视眼的作用。我们证明，细胞因子稀释，通过增加介质体积，显着减少细胞覆盖在封闭和开放胶囊袋模型。这与细胞密度降低和肌成纤维细胞形成相吻合。27种细胞因子的筛选确定了9种候选细胞因子，其表达谱与生长相关。特别是，VEGF被发现调节细胞存活、生长和肌成纤维细胞的形成。VEGF提供了进一步控制PCO发展的治疗靶点，当与开袋IOL设计结合使用时将获得最佳效果。
Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs.