Lewis G P, Linberg K A, Geller S F, Guérin C J, Fisher S K
Neuroscience Research Institute, University of California, Santa Barbara 93106, USA.
Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1530-44.
To examine the effects of brain-derived neurotrophic factor (BDNF) in an animal model of retinal detachment.
Cat retinas were detached from the retinal pigment epithelium for either 7 or 28 days. Animals received either an intravitreal injection of BDNF (100 ILg) or phosphate-buffered saline (PBS), the vehicle for BDNF. Retinas were evaluated using morphology and immunocytochemistry. The width of the outer segment zone was measured, and the retinas were evaluated for changes in protein expression by labeling with antibodies to rod opsin, phosducin, synaptophysin, calbindin D, and glial fibrillary acidic protein (GFAP). The effect of BDNF on both proliferation and apoptotic cell death was examined.
Although there was variability in the treated retinas, most of the animals receiving BDNF had well-organized outer segments that were longer than those in vehicle-treated controls. Immunocytochemistry revealed that treated retinas had consistently less opsin redistribution to the plasma membrane, less phosducin upregulation, and fewer calbindin D-labeled horizontal cell processes. BDNF did not reduce overall cell death in the detachments or death of photoreceptors by apoptosis. However, it significantly reduced the proliferative response of Miller cells and the extent of upregulation of GFAP. CONCLUSIONS. The results suggest that BDNF may aid in the recovery of the retina after reattachment by maintaining the surviving photoreceptor cells, by reducing the gliotic effects in Müller cells, and perhaps by promoting outer segment regeneration.
在视网膜脱离动物模型中研究脑源性神经营养因子(BDNF)的作用。
将猫的视网膜与视网膜色素上皮分离7天或28天。动物接受玻璃体内注射BDNF(100μg)或磷酸盐缓冲盐水(PBS,BDNF的载体)。使用形态学和免疫细胞化学方法评估视网膜。测量外段区域的宽度,并用视杆视蛋白、转导蛋白、突触素、钙结合蛋白D和胶质纤维酸性蛋白(GFAP)抗体标记来评估视网膜蛋白表达的变化。研究BDNF对增殖和凋亡性细胞死亡的影响。
尽管治疗后的视网膜存在差异,但大多数接受BDNF治疗的动物外段结构良好,且比接受载体治疗的对照组更长。免疫细胞化学显示,治疗后的视网膜视蛋白向质膜的重新分布持续减少,转导蛋白上调减少,钙结合蛋白D标记的水平细胞突起减少。BDNF并没有降低脱离视网膜中的总体细胞死亡或光感受器的凋亡性死亡。然而,它显著降低了米勒细胞的增殖反应和GFAP的上调程度。结论。结果表明,BDNF可能通过维持存活的光感受器细胞、减少米勒细胞的胶质化作用以及可能促进外段再生,有助于视网膜复位后的恢复。