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

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.