Lewis Geoffrey P, Sethi Charanjit S, Carter Katrina M, Charteris David G, Fisher Steven K
Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
Mol Vis. 2005 Jul 13;11:491-500.
To compare the activation of microglia in response to retinal detachment in four species.
Experimental detachments were created in cats, rabbits, and ground squirrels and the retinas harvested 1, 3, 7, or 28 days later. Retinal reattachments of 28 days in duration were also performed in cats following a 3-day detachment. Human tissue was obtained during reattachment surgery. Microglia and macrophages were labeled with the lectins Griffonia simplicifolia and Ricinus communis and the antibody CD11b. Müller cell and photoreceptor responses were followed immunocytochemically on the same tissue sections labeled with microglial markers. Images were collected by laser scanning confocal microscopy.
Lightly labeled microglia were observed primarily in the inner retina of control tissue. In the cat and rabbit, a progressive increase in the number of labeled cells occurred in the outer retina beginning at 1 day of detachment. In both long term human and cat detachments numbers of microglia were elevated throughout the retina. This is in contrast to the rabbit and ground squirrel retinas where microglial activation was dramatically diminished in longer term detachments. Presumptive macrophages (anti-CD11b labeled cells) occurred only in the subretinal space. Retinal reattachment in cats significantly attenuated the response except in areas of poor outer segment regeneration.
The robust microglial response to retinal detachment is an indicator of the importance of this cell type in the overall response of the retina. Our data suggest that the feline retina is a particularly appropriate model system for understanding this response in humans. Inhibiting the microglial response in that species should help us understand more precisely its potential role in photoreceptor survival in human pathology.
比较四种物种视网膜脱离后小胶质细胞的激活情况。
在猫、兔和地松鼠中制造实验性视网膜脱离,1、3、7或28天后收获视网膜。在猫中,3天视网膜脱离后还进行了为期28天的视网膜复位。在视网膜复位手术期间获取人体组织。用凝集素单叶豆凝集素和蓖麻凝集素以及抗体CD11b标记小胶质细胞和巨噬细胞。在标记有小胶质细胞标志物的同一组织切片上,通过免疫细胞化学方法追踪米勒细胞和光感受器的反应。通过激光扫描共聚焦显微镜收集图像。
在对照组织的视网膜内层主要观察到轻度标记的小胶质细胞。在猫和兔中,从脱离第1天开始,视网膜外层标记细胞数量逐渐增加。在长期的人体和猫视网膜脱离中,整个视网膜的小胶质细胞数量均升高。这与兔和地松鼠的视网膜形成对比,在兔和地松鼠的视网膜中,长期脱离时小胶质细胞的激活显著减少。推测的巨噬细胞(抗CD11b标记的细胞)仅出现在视网膜下间隙。猫的视网膜复位显著减弱了反应,但在外段再生不良的区域除外。
小胶质细胞对视网膜脱离的强烈反应表明该细胞类型在视网膜整体反应中的重要性。我们的数据表明,猫视网膜是理解人类这种反应的特别合适的模型系统。抑制该物种的小胶质细胞反应应有助于我们更准确地了解其在人类病理学中对光感受器存活的潜在作用。