PMID- 18660427
OWN - NLM
STAT- MEDLINE
DCOM- 20080812
LR  - 20131121
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 49
IP  - 8
DP  - 2008 Aug
TI  - Topical doxycycline can induce expression of BDNF in transduced retinal pigment 
      epithelial cells transplanted into the subretinal space.
PG  - 3631-9
LID - 10.1167/iovs.07-0947 [doi]
AB  - PURPOSE: To determine whether topical doxycycline (DOX) induces the expression of 
      brain-derived neurotrophic factor (BDNF) by BDNF-transduced retinal pigment 
      epithelial (RPE) cells transplanted into the subretinal space of rats. METHODS: A 
      rat RPE cell line that can express BDNF by exposure to DOX was created 
      (Tet-BDNF-RPE). The expression of BDNF was examined by ELISA, Western blot 
      analysis, and real-time PCR. The expression of BDNF was controlled by exposure to 
      DOX in vitro. Tet-BDNF-RPE cells were transplanted into the subretinal space of 
      rats, and the rats were exposed to constant light 1 day or 1 month after the 
      transplantation. The rats were followed with or without topical DOX and examined 
      electrophysiologically and histologically. RESULTS: The expression of BDNF was 
      upregulated by exposure of Tet-BDNF-RPE cells to DOX in vitro. The optimal 
      concentration for inducing BDNF expression was 0.5 to 1.0 microg/mL DOX. BDNF 
      expression was also increased in vivo by topical DOX after subretinal 
      transplantation of Tet-BDNF-RPE cells. Statistically significant protection of 
      the electroretinogram amplitudes were found 3 days or 1 month after 
      transplantation, and the outer nuclear layer was better preserved 7 days or 1 
      month after transplantation in the rats treated by 5 or 10 mg/mL/d topical DOX 
      than rats treated by other conditions or sham-operation rats. CONCLUSIONS: The 
      expression of BDNF can be significantly increased by topical DOX after 
      Tet-BDNF-RPE subretinal transplantation. Better photoreceptor protection against 
      phototoxicity was achieved by DOX eye drops after the cell transplantation.
FAU - Abe, Toshiaki
AU  - Abe T
AD  - Division of Clinical Cell Therapy, Translational and Advanced Animal Research, 
      Tohoku University Graduate School of Medicine, Miyagi, Sendai, Japan. 
      toshi@oph.med.tohoku.ac.jp
FAU - Wakusawa, Ryosuke
AU  - Wakusawa R
FAU - Seto, Haruka
AU  - Seto H
FAU - Asai, Nobuharu
AU  - Asai N
FAU - Saito, Takae
AU  - Saito T
FAU - Nishida, Kohji
AU  - Nishida K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Lipids)
RN  - 0 (Lipofectamine)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (RNA, Messenger)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Administration, Topical
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cell Line
MH  - Cell Survival
MH  - Cell Transplantation
MH  - Doxycycline/*administration & dosage
MH  - Electroretinography
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression
MH  - Lipids
MH  - Male
MH  - Ophthalmic Solutions/administration & dosage
MH  - Pigment Epithelium of Eye/*metabolism/*transplantation
MH  - RNA, Messenger/metabolism
MH  - Radiation Injuries, Experimental/metabolism/*prevention & control/surgery
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retina/radiation effects
MH  - Retinal Degeneration/metabolism/*prevention & control/surgery
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transfection
MH  - Up-Regulation
EDAT- 2008/07/29 09:00
MHDA- 2008/08/13 09:00
CRDT- 2008/07/29 09:00
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2008/08/13 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
AID - 49/8/3631 [pii]
AID - 10.1167/iovs.07-0947 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3631-9. doi: 10.1167/iovs.07-0947.