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Invest Ophthalmol Vis Sci. 2005 Feb;46(2):669-73.

Role of neurotrophin-4/5 in neural cell death during retinal development and ischemic retinal injury in vivo.

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Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.



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.


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.


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.


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.

[Indexed for MEDLINE]

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