The Role of Angiotensin II Receptor Subtype in Ocular Injury

血管紧张素II （angii）在调节心血管结构和血流动力学中起重要作用。两种主要的Ang II受体亚型，称为1型（AT_1）和2型（AT_2）受体，先前已报道过。最近的研究表明，Ang II通过这些受体调节伤口愈合过程。我们利用眼外伤愈合模型研究了AT_1和AT_2受体亚型在眼外伤中的作用。结膜下创面愈合：以野生型雄性（WT; C57BL/6J）、AT_<1a> null （AT_<1a>KO）和AT_2 null （AT_2KO）小鼠为实验对象，采用结膜下钝性夹层建立创面愈合模型。结膜下损伤诱导胶原沉积。损伤后14 d， AT_2KO小鼠结膜下胶原沉积高于WT小鼠，而AT_<1a>KO小鼠结膜下胶原沉积低于WT小鼠。损伤后第7天，包括结膜在内的结膜下组织中1型胶原mRNA水平升高。AT_2KO小鼠的这一增幅明显高于AT_<1a>KO小鼠，但低于WT小鼠。为了研究AT1和AT2受体在胶原合成调控中的作用机制，我们检测了TIMP-1的表达。结膜下损伤后12小时mRNA水平升高。然而，TIMP-1的表达在AT_<1a>KO小鼠中明显升高，但在AT_2KO小鼠中低于WT小鼠。角膜上皮创面愈合：采用准分子扎扎法建立雄性WT和AT_<1a>KO小鼠角膜上皮创面愈合模型。与WT小鼠相比，AT_<1a>的KO小鼠角膜上皮伤口愈合延迟。AT_<1a>KO小鼠上皮细胞BrdU指数低于WT小鼠。提示AT_1和AT2受体亚型在眼损伤的调控中起重要作用。

Angiotensin II (Ang II) plays an important role in the regulation of cardiovascular structure and hemodynamics. Two major Ang II receptor subtypes, named type 1 (AT_1) and type 2 (AT_2) receptors, have been previously reported. Recent studies suggest that Ang II regulates wound healing process through these receptors. However, the detailed mechanism is not clarified We investigated the role of AT_1 and AT_2 receptor subtypes in ocular injury using wound healing model.1.Subconjunctival wound healing : Wound healing model was developed by subconjuncival blunt dissection in male wild type (WT ; C57BL/6J), AT_<1a> null (AT_<1a>KO) and AT_2 null (AT_2KO) mice. Subconjunctival injury induced collagen deposition. Subconjunctival collagen deposition detected by histological analysis at 14 days after injury was higher in AT_2KO mice than in WT mice, but it was lower than in AT_<1a>KO mice than in WT mice. The level of mRNA for type 1 collagen at 7 days was increased in subconjunctival tissue including conjunctiva after injury. This increase was significantly higher in AT_2KO mice, but it was lower than in AT_<1a>KO mice than in WT mice. To examine the mechanism of action of AT1 and AT2 receptors on collagen synthesis regulation, we assayed the expression of TIMP-1. The level of mRNA was also increased at 12 hours after injury after subconjuntival damage. However, the increase in TIMP-1 expression was significantly higher in AT_<1a>KO mice, but lower than in AT_2KO mice than in WT mice.2. Corneal epithelial wound healing : Corneal epithelial wound healing model was made by eximer lazar in male WT and AT_<1a>KO mice. AT_<1a>KO mice delayed corneal epithelial wound healing compared to WT mice. The BrdU index in epithelial cells was lower in the AT_<1a>KO mice than in the WT mice.These results suggest that AT_1 and AT2 receptor subtypes play an important role in the regulation of ocular injury.