Jomary C, Thomas M, Grist J, Milbrandt J, Neal M J, Jones S E
Department of Pharmacology, The Rayne Institute, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, United Kingdom.
Invest Ophthalmol Vis Sci. 1999 Mar;40(3):568-74.
Neurturin (NTN) and its receptor components (GFRalpha2 and Ret) play an important role in the survival of different populations of neurons in the central and peripheral nervous systems. To gain insight into their possible functions throughout normal retinal development and during retinal neuronal apoptosis, the retinal distribution of expression of NTN and GFRalpha2 mRNAs and Ret protein were compared in control and retinal degeneration (rd) mice.
Eyes from control and rd animals were fixed in paraformaldehyde before sectioning. For in situ hybridization, retinal sections were hybridized with 35S-radiolabeled sense and antisense riboprobes for murine NTN and GFRalpha2 and were autoradiographed. Ret localization was detected by immunofluorescence.
Neurturin mRNA expression was modulated through normal postnatal retinal development and was localized primarily to the inner retina and photoreceptor outer segments. GFRalpha2 mRNA displayed a diffuse developmental pattern of expression, but in the mature normal retina, NTN and GFRalpha2 mRNAs were more closely colocalized. Ret protein was localized particularly at the outer segments of photoreceptors, inner retina, and ganglion cell layers, but there were no prominent differences among genotypes. Increased NTN mRNA expression was detected in the retinal pigment epithelium and neural retina in concert with photoreceptor degeneration in rd mouse. In contrast, the level of GFRalpha2 mRNA was lower in rd compared with that in normal retina.
These results suggest that NTN and its receptor are involved in retinal postnatal development and maintenance and that alterations in their transcription patterns are associated with inherited retinal degeneration.
神经营养因子（NTN）及其受体成分（GFRalpha2和Ret）在中枢和外周神经系统中不同神经元群体的存活中发挥重要作用。为深入了解它们在正常视网膜发育以及视网膜神经元凋亡过程中的可能功能，我们比较了正常小鼠和视网膜变性（rd）小鼠中NTN和GFRalpha2 mRNA以及Ret蛋白的视网膜表达分布。
将正常和rd小鼠的眼睛在切片前用多聚甲醛固定。对于原位杂交，视网膜切片与用于小鼠NTN和GFRalpha2的35S放射性标记的正义和反义核糖探针杂交并进行放射自显影。通过免疫荧光检测Ret的定位。
神经营养因子mRNA的表达在出生后正常视网膜发育过程中受到调节，主要定位于视网膜内层和光感受器外段。GFRalpha2 mRNA呈现出弥散的发育表达模式，但在成熟的正常视网膜中，NTN和GFRalpha2 mRNA的共定位更为紧密。Ret蛋白特别定位于光感受器的外段、视网膜内层和神经节细胞层，但不同基因型之间没有明显差异。在rd小鼠中，随着光感受器变性，在视网膜色素上皮和神经视网膜中检测到神经营养因子mRNA表达增加。相比之下，rd小鼠中GFRalpha2 mRNA的水平低于正常视网膜。
这些结果表明，神经营养因子及其受体参与视网膜出生后的发育和维持，并且它们转录模式的改变与遗传性视网膜变性有关。
