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The roles of α V integrins in lens EMT and posterior capsular opacification
Author(s) -
Mamuya Fahmy A.,
Wang Yan,
Roop Victoria H.,
Scheiblin David A.,
Zajac Jocelyn C.,
Duncan Melinda K.
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12213
Subject(s) - integrin , lens (geology) , microbiology and biotechnology , biology , genetics , receptor , paleontology
Posterior capsular opacification ( PCO ) is the major complication arising after cataract treatment. PCO occurs when the lens epithelial cells remaining following surgery ( LC s) undergo a wound healing response producing a mixture of α‐smooth muscle actin (α‐ SMA )‐expressing myofibroblasts and lens fibre cells, which impair vision. Prior investigations have proposed that integrins play a central role in PCO and we found that, in a mouse fibre cell removal model of cataract surgery, expression of α V integrin and its interacting β‐subunits β1, β5, β6, β8 are up‐regulated concomitant with α‐ SMA in LC s following surgery. To test the hypothesis that α V integrins are functionally important in PCO pathogenesis, we created mice lacking the α V integrin subunit in all lens cells. Adult lenses lacking α V integrins are transparent and show no apparent morphological abnormalities when compared with control lenses. However, following surgical fibre cell removal, the LC s in control eyes increased cell proliferation, and up‐regulated the expression of α‐ SMA , β1‐integrin, fibronectin, tenascin‐C and transforming growth factor beta ( TGF ‐β)–induced protein within 48 hrs, while LC s lacking α V integrins exhibited much less cell proliferation and little to no up‐regulation of any of the fibrotic markers tested. This effect appears to result from the known roles of α V integrins in latent TGF ‐β activation as α V integrin null lenses do not exhibit detectable SMAD ‐3 phosphorylation after surgery, while this occurs robustly in control lenses, consistent with the known roles for TGF ‐β in fibrotic PCO . These data suggest that therapeutics antagonizing α V integrin function could be used to prevent fibrotic PCO following cataract surgery.

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