Johnson L V, Ozaki S, Staples M K, Erickson P A, Anderson D H
Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara 93106, USA.
Exp Eye Res. 2000 Apr;70(4):441-9. doi: 10.1006/exer.1999.0798.
Drusen are abnormal extracellular deposits that accumulate between the retinal pigmented epithelium and Bruch's membrane and are commonly associated with age-related macular degeneration. Our recent work has identified a number of plasma proteins as molecular components of drusen. Of interest is the fact that many of these drusen-associated molecules are acute phase reactant proteins and some have established roles in mediating immune responsiveness. As immune and inflammatory responses appear to play a role in the formation of other pathologic age-related deposits, we examined the distribution of immunoglobulin molecules and terminal complement complexes at sites of drusen deposition. Here, we report that concentrations of immunoglobulin G and terminal C5b-9 complement complexes are present in drusen. In addition, we observe that retinal pigmented epithelial cells overlying or directly adjacent to drusen, as well as some within apparently normal epithelia, exhibit cytoplasmic immunoreactivity for immunoglobulin and the C5 component of complement. Taken together, these results suggest that drusen biogenesis may be a byproduct of immune responsiveness, and they implicate immune complex-mediated pathogenesis involving retinal pigmented epithelial cells as an initiating event in drusen formation.
玻璃膜疣是异常的细胞外沉积物，积聚在视网膜色素上皮和布鲁赫膜之间，通常与年龄相关性黄斑变性有关。我们最近的研究工作已鉴定出多种血浆蛋白作为玻璃膜疣的分子成分。有趣的是，许多这些与玻璃膜疣相关的分子都是急性期反应蛋白，并且其中一些在介导免疫反应中已确立了作用。由于免疫和炎症反应似乎在其他与年龄相关的病理性沉积物的形成中发挥作用，我们研究了免疫球蛋白分子和终末补体复合物在玻璃膜疣沉积部位的分布。在此，我们报告玻璃膜疣中存在免疫球蛋白G和终末C5b-9补体复合物的浓度。此外，我们观察到覆盖玻璃膜疣或与其直接相邻的视网膜色素上皮细胞，以及一些明显正常上皮内的细胞，对免疫球蛋白和补体C5成分表现出细胞质免疫反应性。综上所述，这些结果表明玻璃膜疣的形成可能是免疫反应的副产品，并且它们暗示涉及视网膜色素上皮细胞的免疫复合物介导的发病机制是玻璃膜疣形成的起始事件。
