Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration.
Prolonged or high-intensity exposure to visible light leads to photoreceptor cell death. In this study, we demonstrate a novel pathway of light-induced photoreceptor apoptosis involving the low-affinity neurotrophin receptor p75 (p75NTR). Retinal degeneration upregulated both p75NTR and the high-affinity neurotrophin receptor TrkC in different parts of Müller glial cells. Exogenous neurotrophin-3 (NT-3) increased, but nerve growth factor (NGF) decreased basic fibroblast growth factor (bFGF) production in Müller cells, which can directly rescue photoreceptor apoptosis. Blockade of p75NTR prevented bFGF reduction and resulted in both structural and functional photoreceptor survival in vivo. Furthermore, the absence of p75NTR significantly prevented light-induced photoreceptor apoptosis. These observations implicate glial cells in the determination of neural cell survival, and suggest functional glial-neuronal cell interactions as new therapeutic targets for neurodegeneration.
Harada
T
T
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. harada@ncnp.go.jp
Harada
C
C
Nakayama
N
N
Okuyama
S
S
Yoshida
K
K
Kohsaka
S
S
Matsuda
H
H
Wada
K
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D011833:Radiation Injuries, Experimental; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000235:genetics; D020812:Receptor, trkC / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D016222:Fibroblast Growth Factor 2; D020812:Receptor, trkC