TrkB-T1 receptors on Muller cells play critical role in brain-derived neurotrophic factor-mediated photoreceptor protection against phototoxicity.
OBJECTIVE
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 x 10(7) 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. TrkB-T1 was slightly upregulated by Western blot, and one of the cells that upregulated TrkB-T1 was Muller cells by immunohistochemistry.


CONCLUSIONS
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.
Saito
Takae
T
Division of Clinical Cell Therapy, Center for Translational and Advanced Animal Research, Miyagi, Japan.
Abe
Toshiaki
T
Wakusawa
Ryosuke
R
Sato
Hajime
H
Asai
Harunobu
H
Tokita-Ishikawa
Yumi
Y
Nishida
Kohji
K
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D017690:Cell Transplantation; D000229:Dependovirus / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D007150:Immunohistochemistry; D007498:Iris / Q000166:cytology; D008027:Light / Q000009:adverse effects; D009457:Neuroglia / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000528:radiation effects*; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000637:transplantation; D034741:RNA, Small Interfering / Q000502:physiology; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000502:physiology*; D012162:Retinal Degeneration / Q000209:etiology / Q000517:prevention & control*; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D034741:RNA, Small Interfering; D020813:Receptor, trkB