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

Invest Ophthalmol Vis Sci. 2005 Feb;46(2):669-73. doi: 10.1167/iovs.04-0826.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Brain-Derived Neurotrophic Factor / physiology
  • Cytoprotection
  • Mice
  • Mice, Knockout
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology*
  • Neurons / pathology*
  • RNA, Messenger / metabolism
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Retina / growth & development*
  • Retinal Diseases / metabolism*
  • Retinal Diseases / pathology
  • Reverse Transcriptase Polymerase Chain Reaction


  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • RNA, Messenger
  • neurotrophin 5
  • neurotrophin 4