Fujieda Hiroki, Sasaki Hiroshi
Department of Anatomy, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Exp Eye Res. 2008 Feb;86(2):335-43. doi: 10.1016/j.exer.2007.11.005. Epub 2007 Nov 17.
Brain-derived neurotrophic factor (BDNF) regulates many aspects of neuronal development, including survival, axonal and dendritic growth and synapse formation. Despite recent advances in our understanding of the functional significance of BDNF in retinal development, the retinal cell types expressing BDNF remains poorly defined. The goal of the present study was to determine the localization of BDNF in the mammalian retina, with special focus on the subtypes of amacrine cells, and to characterize, at the cellular level, the effects of constant light exposure during early postnatal period on retinal expression of BDNF. Retinas from 3-week-old rats reared in a normal light cycle or constant light were subjected to double immunofluorescence staining using antibodies to BDNF and retinal cell markers. BDNF immunoreactivity was localized to ganglion cells, cholinergic amacrine cells and dopaminergic amacrine cells, but not to AII amacrine cells regardless of rearing conditions. Approximately 75% of BDNF-positive cells in the inner nuclear layer were cholinergic amacrine cells in animals reared in a normal lighting condition. While BDNF immunoreactivity in ganglion cells and cholinergic amacrine cells was significantly increased by constant light rearing, which in dopaminergic amacrine cells was apparently unaltered. The overall structure of the retina and the density of ganglion cells, cholinergic amacrine cells and AII amacrine cells were unaffected by rearing conditions, whereas the density of dopaminergic amacrine cells was significantly increased by constant light rearing. The present results indicate that cholinergic amacrine cells are the primary source of BDNF in the inner nuclear layer of the rat retina and provide the first evidence that cholinergic amacrine cells may be involved in the visual activity-dependent regulation of retinal development through the production of BDNF. The present data also suggest that the production or survival of dopaminergic amacrine cells is regulated by early visual experience.
脑源性神经营养因子（BDNF）调节神经元发育的多个方面，包括存活、轴突和树突生长以及突触形成。尽管最近我们对BDNF在视网膜发育中的功能意义有了进一步了解，但表达BDNF的视网膜细胞类型仍不清楚。本研究的目的是确定BDNF在哺乳动物视网膜中的定位，特别关注无长突细胞的亚型，并在细胞水平上表征出生后早期持续光照对视网膜BDNF表达的影响。对在正常光照周期或持续光照下饲养的3周龄大鼠的视网膜，使用抗BDNF抗体和视网膜细胞标志物进行双重免疫荧光染色。无论饲养条件如何，BDNF免疫反应性定位于神经节细胞、胆碱能无长突细胞和多巴胺能无长突细胞，但不定位于AII无长突细胞。在正常光照条件下饲养的动物中，内核层中约75%的BDNF阳性细胞是胆碱能无长突细胞。虽然持续光照饲养显著增加了神经节细胞和胆碱能无长突细胞中的BDNF免疫反应性，但多巴胺能无长突细胞中的BDNF免疫反应性明显未改变。视网膜的整体结构以及神经节细胞、胆碱能无长突细胞和AII无长突细胞的密度不受饲养条件的影响，而持续光照饲养显著增加了多巴胺能无长突细胞的密度。目前的结果表明，胆碱能无长突细胞是大鼠视网膜内核层中BDNF的主要来源，并提供了第一个证据，即胆碱能无长突细胞可能通过产生BDNF参与视觉活动依赖的视网膜发育调节。目前的数据还表明，多巴胺能无长突细胞的产生或存活受早期视觉经验的调节。
