Citation:Dong Y,Dong Z,Kase S,Ando R,Fukuhara J,Kinoshita S,Inafuku S,Tagawa Y,Ishizuka ET,Saito W,Murata M,Kanda A,Noda K,Ishida S.Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy.Int J Ophthalmol 2016;9(8):1100-1105,doi:10.18240/ijo.2016.08.03
Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy
Received:September 10, 2015  Revised:December 24, 2015
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DOI:10.18240/ijo.2016.08.03
Key Words:phosphorylated alphaB-crystallin  vascular endothelial growth factor  neovascularization  proliferative diabetic retinopathy
Fund Project:Supported by the Research foundation of the Japan Society for the Promotion of Science (JSPS) (No.15K10856); Scientific Research from The Ministry of Education, Culture, Sports, Science, and Technology (MEXT).
                                         
AuthorInstitution
Yoko Dong Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Zhenyu Dong Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Satoru Kase Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Ryo Ando Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Junichi Fukuhara Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Satoshi Kinoshita Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Saori Inafuku Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Yoshiaki Tagawa Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Erdal Tan Ishizuka Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Wataru Saito Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Miyuki Murata Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Atsuhiro Kanda Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Kousuke Noda Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
Susumu Ishida Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Kita-ku, Sapporo 060-8638, Hokkaido, Japan
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Abstract:
      AIM: To examine phosphorylation of alphaB-crystallin (p-?BC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-?BC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR).

    METHODS: Eleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-?BC, VEGF, CD31, and p-p38 MAPK antibodies.

    RESULTS: Immunoreactivity for p-?BC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-?BC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-?BC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes.

    CONCLUSION: Phosphorylation of ?BC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.

PMC FullText Html:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990572/
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