TY - JOUR
T1 - TrkB-T1 receptors on muller cells play critical role in brain-derived neurotrophic factor-mediated photoreceptor protection against phototoxicity
AU - Saito, Takae
AU - Abe, Toshiaki
AU - Wakusawa, Ryosuke
AU - Sato, Hajime
AU - Asai, Harunobu
AU - Tokita-Ishikawa, Yumi
AU - Nishida, Kohji
N1 - Funding Information:
This work was supported in part by grants from Grant-in Aid for Scientific Research 14370553, 17659542, 18659508 (Abe, T.).
PY - 2009
Y1 - 2009
N2 - Purpose: To determine how brain-derived neurotrophic factor (BDNF) protects photoreceptors against phototoxicity. Methods: Iris pigment epithelial cells (IPE) that were transduced with different concentrations of adeno-associated virus (AAV) mediated BDNF (AAV-BDNF-IPE) were transplanted into the subretinal space of rats. We also injected small interfering RNAs (siRNAs) for TrkB, a BDNF receptor. The rats were exposed to continuous light to induce phototoxicity. We examined the expression of TrkB in the retina by Western blot and immunohistochemistry. Results: Significant photoreceptor protection was detected when more than 1 × 107 capsids/ml AAV-BDNF was transplanted. An intravitreal injection of siRNAs showed that the photoreceptor protection by AAV-BDNF-IPE was reduced by injecting the siRNA of TrkB-T1, one of the TrkB isoforms. TrkBT1 was slightly upregulated by Western blot, and one of the cells that upregulated TrkB-T1 was Muller cells by immunohistochemistry. Conclusion: We conclude that Muller cells are one of the cells responsible for the expression of TrkBs, and TrkB-T1 may play a role in the protection of photoreceptors against phototoxicity.
AB - Purpose: To determine how brain-derived neurotrophic factor (BDNF) protects photoreceptors against phototoxicity. Methods: Iris pigment epithelial cells (IPE) that were transduced with different concentrations of adeno-associated virus (AAV) mediated BDNF (AAV-BDNF-IPE) were transplanted into the subretinal space of rats. We also injected small interfering RNAs (siRNAs) for TrkB, a BDNF receptor. The rats were exposed to continuous light to induce phototoxicity. We examined the expression of TrkB in the retina by Western blot and immunohistochemistry. Results: Significant photoreceptor protection was detected when more than 1 × 107 capsids/ml AAV-BDNF was transplanted. An intravitreal injection of siRNAs showed that the photoreceptor protection by AAV-BDNF-IPE was reduced by injecting the siRNA of TrkB-T1, one of the TrkB isoforms. TrkBT1 was slightly upregulated by Western blot, and one of the cells that upregulated TrkB-T1 was Muller cells by immunohistochemistry. Conclusion: We conclude that Muller cells are one of the cells responsible for the expression of TrkBs, and TrkB-T1 may play a role in the protection of photoreceptors against phototoxicity.
KW - Brain-derived neurotrophic factor
KW - Muller cells
KW - Phototoxicity
KW - Transplantation
KW - TrkB-T1
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U2 - 10.1080/02713680902972358
DO - 10.1080/02713680902972358
M3 - Article
C2 - 19899971
AN - SCOPUS:70350676617
SN - 0271-3683
VL - 34
SP - 580
EP - 588
JO - Current Eye Research
JF - Current Eye Research
IS - 7
ER -