Tomasek James J, Haaksma Carol J, Schwartz Robert J, Vuong Duc T, Zhang Sarah X, Ash John D, Ma Jian-xing, Al-Ubaidi Muayyad R
Departments of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2693-700. doi: 10.1167/iovs.05-1297.
Vascular smooth muscle (SM) cells and pericytes are essential for normal vascular development. SM alpha-actin null mice were used to determine whether vascular SM and pericyte contractile functions, and not merely their presence, are necessary for vascular development, normal blood-retina barrier (BRB) permeability, and retinal function.
Age-matched SM alpha-actin null and wild-type mice were analyzed. Retinal structure, vascular pattern, and SM cell and pericyte distribution were analyzed histologically. Retinal vascular permeability (RVP) was measured with the Evans blue dye method. Electroretinography (ERG) was performed to evaluate retinal function.
Deletion of SM alpha-actin did not result in any alterations in retinal morphology, vascular pattern, or SM cell and pericyte ensheathing of vessels in SM alpha-actin null mice. A significant increase in RVP was observed in SM alpha-actin null mice at both postnatal day (P)50 and P75 (P<0.05 and P<0.001, respectively). ERG analysis demonstrated a significant reduction in both rod and cone function in SM alpha-actin null mice at P22, P45, and P75 (P<0.01 at all ages).
These results demonstrate that SM alpha-actin in SM cells and pericytes is not necessary for the formation of a normal retinal vascular pattern; however, SM alpha-actin is necessary for SM cells and pericytes to interact with endothelial cells to form a fully functional BRB. These results are important in understanding the role of contractile gene expression in the maintenance and function of the BRB and may provide a model for studying pathologic conditions, such as diabetes, that alter the function of this barrier.
血管平滑肌（SM）细胞和周细胞对正常血管发育至关重要。利用SMα-肌动蛋白基因敲除小鼠来确定血管SM和周细胞的收缩功能，而不仅仅是它们的存在，对于血管发育、正常血视网膜屏障（BRB）通透性和视网膜功能是否必要。
对年龄匹配的SMα-肌动蛋白基因敲除小鼠和野生型小鼠进行分析。通过组织学方法分析视网膜结构、血管模式以及SM细胞和周细胞的分布。采用伊文思蓝染料法测量视网膜血管通透性（RVP）。进行视网膜电图（ERG）检查以评估视网膜功能。
在SMα-肌动蛋白基因敲除小鼠中，SMα-肌动蛋白的缺失并未导致视网膜形态、血管模式或血管周围SM细胞和周细胞包绕出现任何改变。在出生后第（P）50天和P75天，SMα-肌动蛋白基因敲除小鼠的RVP均显著增加（分别为P<0.05和P<0.001）。ERG分析表明，在P22、P45和P75时，SMα-肌动蛋白基因敲除小鼠的视杆和视锥功能均显著降低（各年龄组P<0.01）。
这些结果表明，SM细胞和周细胞中的SMα-肌动蛋白对于正常视网膜血管模式的形成并非必需；然而，SMα-肌动蛋白对于SM细胞和周细胞与内皮细胞相互作用以形成功能完整的BRB是必需的。这些结果对于理解收缩基因表达在BRB维持和功能中的作用具有重要意义，并且可能为研究改变该屏障功能的病理状况（如糖尿病）提供一个模型。
