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Neuroprotective response after photodynamic therapy : Role of vascular endothelial growth factor

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Title: Neuroprotective response after photodynamic therapy : Role of vascular endothelial growth factor
Authors: Suzuki, Misa Browse this author
Ozawa, Yoko Browse this author
Kubota, Shunsuke Browse this author
Hirasawa, Manabu Browse this author
Miyake, Seiji Browse this author
Noda, Kousuke Browse this author →KAKEN DB
Tsubota, Kazuo Browse this author
Kadonosono, Kazuaki Browse this author
Ishida, Susumu Browse this author →KAKEN DB
Keywords: VEGF
PDT
retina
neuroprotection
Akt
BAX
Issue Date: 16-Dec-2011
Publisher: BioMed Central
Journal Title: Journal of Neuroinflammation
Volume: 8
Issue: 1
Start Page: 176
Publisher DOI: 10.1186/1742-2094-8-176
PMID: 22171708
Abstract: Background: Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in tumors and age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood. Methods: We assessed VEGF levels after PDT of normal mouse retinal tissue, using a laser duration that did not cause obvious tissue damage. To determine the role of PDT-induced VEGF and its downstream signaling, we intravitreally injected a VEGF inhibitor, VEGFR1 Fc, or a PI3K/Akt inhibitor, LY294002, immediately after PDT. Then, histological and biochemical changes of the retinal tissue were analyzed by immunohistochemistry and immunoblot analyses, respectively. Results: At both the mRNA and protein levels, VEGF was upregulated immediately and transiently after PDT. VEGF suppression after PDT resulted in apoptotic destruction of the photoreceptor cell layer in only the irradiated area during PDT. Under these conditions, activation of the anti-apoptotic molecule Akt was suppressed in the irradiated area, and levels of the pro-apoptotic protein BAX were increased. Intravitreal injection of a PI3K/Akt inhibitor immediately after PDT increased BAX levels and photoreceptor cell apoptosis. Conclusion: Cytotoxic stress caused by PDT, at levels that do not cause overt tissue damage, induces VEGF and activates Akt to rescue the neural tissue, suppressing BAX. Thus, the immediate and transient induction of VEGF after PDT is neuroprotective.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/54622
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石田 晋

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