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Chikako Harada, Takayuki Harada, Hun-Meng A. Quah, Kazuhiko Namekata, Kazuhiko Yoshida, Shigeaki Ohno, Kohichi Tanaka, Luis F. Parada; Role of Neurotrophin-4/5 in Neural Cell Death during Retinal Development and Ischemic Retinal Injury In Vivo. Invest. Ophthalmol. Vis. Sci. 2005;46(2):669-673. doi: 10.1167/iovs.04-0826.
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purpose. Neurotrophin (NT)-4/5 and brain-derived neurotrophic factor (BDNF) mediate cell survival through TrkB, a high-affinity tyrosine kinase receptor, and may prevent neural cell death in various pathologic conditions. This study was conducted to investigate the function of NT-4/5 in neural cell death during retinal development and ischemic retinal injury.
methods. Retinal development in wild-type, NT-4/5 knockout (KO), and NT-4/5:BDNF double-KO mice was histologically examined from postnatal day 0 (P0) to P90. Ischemic retinal injury was performed at P42, and NT-4/5 mRNA expression level and the extent of retinal cell death was quantitatively examined.
results. Real-time PCR analysis revealed increased NT-4/5 mRNA expression in the ischemic retina. In the NT-4/5 KO mouse, retinal development and structure were normal, but the strain was susceptible to ischemic injury on P42. In contrast, NT-4/5:BDNF double-KO mice showed delayed retinal development and died before P42.
conclusions. These results suggest that NT-4/5, in combination with other trophic factors, is involved in the postnatal survival of retinal neurons during both development and degeneration.
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