睫状神经营养因子及其受体在正常及变性视网膜中表达水平与分布的变化

Expression and distribution of ciliary neurotrophic factor and its receptor in normal and degenerative retina

目的观察正常Sprague-Dawley(SD)和遗传性视网膜变性RoyalCollegeofSurgeons(RCS)大鼠视网膜发育过程中睫状神经营养因子(CNTF)及其受体(CNTFR)的表达水平与分布特点。方法新生至成年(12个月龄)SD和RCS大鼠视网膜石蜡切片,免疫组织化学染色显示睫状神经营养因子及其受体表达水平和分布变化。结果出生后0～7d,SD大鼠神经视网膜全层染色呈阳性,随着周龄增加,节细胞染色明显增强,而其他细胞染色减弱,至28d时节细胞染色达高峰,并持续至老年;RCS大鼠视网膜CNTF免疫组织化学染色结果与SD大鼠基本相同。出生后0～3d,SD大鼠神经视网膜全层CNTFR的表达呈弱阳性,节细胞染色稍深,在将来要发育成外节处可见断续阳性染色;随着周龄增加,光感受器外节处阳性染色逐渐增强,14～28d染色达到高峰;56d时外节染色减弱,而节细胞染色却明显增强,直至老年。3～14dRCS大鼠视网膜CNTFR染色基本与同龄SD大鼠一致,但21d起外节染色明显减弱,28d时外节染色基本呈阴性,但节细胞仍呈强阳性,一直持续到老年。结论CNTF的表达在正常和变性大鼠间无明显差异;CNTFR主要在节细胞和光感受器外节处高水平表达,正常和变性RCS大鼠间存在显著差异,为利用CNTF治疗视网膜变性提供了实验证据。

Objective To investigate the expression and characteristics distribution of ciliary neurotrophic factor （CNTF） and its receptor during the development of retina of healthy Sprague-Dawley （SD）and Royal College of Surgeons （RCS） rats with hereditary retinal degeneration. Methods The expression and distribution of ciliary neurotrophic factor and its receptor were detected by immunohistochemical staining in the retinal paraffin sections of SD and RCS rats from newborn to 12 moths old. Results In the normal retina of SD rats 0-7 days after birth, positive CNTF staining was found in all of the retinal layers and the staining of ganglion cells strengthened and other cells weakened as the age of rats increased ; the staining of ganglion cells reached the peak at the 4th week and lasted till the agedness. The same results of the CNTF staining were also found in RCS rats retina. Weak positive staining of CNTFR in all of the retinal layers was seen in the 0-3-day-old SD rats ; the ganglion cells were darkly stained and incontinuous positive staining at the site which would develop to be the external segment was found; as the age increased, the positive staining of external segment of pbotoreceptor enhanced and reached the peak at the 14-28th day after birth. At the 56th day, the staining of ganglion cells in retina of SD rats was strengthened while the staining of external segment weakened till the agedness. The expression of CNTFR in retina of 3-14-day-old RCS rats was the same as which of normal SD rats basically, but the staining of external segment weakened obviously from the 21st day on, and negative staining of external and positive ganglion cells were detected at the 28th day till the agedness. Conclusions Expression of CNTF in normal SD rats and RCS rats with hereditary retinal degeneration is almost the same. The presence of significant difference of expression of CNTFR between normal SD rats retina and RCS rats retina may provide the experimental gist for the CNTF treatment to retinal degeneration.