Shams N B, Hanninen L A, Chaves H V, Frangieh G, Reddy C V, Azar D T, Kenyon K R
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2646-54.
To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency.
An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen.
Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin.
The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea.
了解维生素A缺乏时角膜上皮易于脱落的潜在机制。
利用维生素A缺乏动物模型——维生素A缺乏大鼠(A-大鼠),采用透射电子显微镜、计算机辅助形态计量分析和间接免疫荧光法,研究大鼠角膜上皮与其基底膜的黏附情况,重点关注半桥粒和类天疱疮抗原等锚定结构的结构和分子组成。
透射电子显微镜观察到基底上皮细胞膜与基底膜之间有大量微小分离,其间有节段性基底膜重复和电子致密沉积物。形态计量分析显示半桥粒的频率和大小在统计学上显著降低。用醋酸视黄酯(700微克/周)补充饮食4周后,可检测到这些相同结构异常的显著逆转。对黏附复合体成分类天疱疮抗原的免疫荧光染色显示,基底上皮细胞质染色强烈,但基底膜染色微弱且不连续。在A-角膜中,层粘连蛋白的染色也很弱。相比之下,正常角膜类天疱疮抗原无细胞质染色,基底膜类天疱疮抗原和层粘连蛋白染色强烈。
作者提出,上皮基底膜复合体的结构异常是导致观察到的上皮黏附松散和脱落的原因,也是维生素A缺乏大鼠角膜愈合过程中其他已知异常的原因。