Role of Decorin in Posterior Capsule Opacification and Eye Lens Development

Shinsuke Shibata, Naoko Shibata, Satoshi Ohtsuka, Yasuo Yoshitomi, Etsuko Kiyokawa, Hideto Yonekura, Dhirendra P. Singh, Hiroshi Sasaki, Eri Kubo

Research output: Contribution to journalArticlepeer-review

Abstract

Decorin (DCN) is involved in a variety of physiological and pathological processes. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) has been proposed as a major cause for the development of posterior capsule opacification (PCO) after cataract surgery. We investigated the plausible target gene(s) that suppress PCO. The expression of Dcn was significantly upregulated in rat PCO tissues compared to that observed in the control using a microarray-based approach. LECs treated with fibroblast growth factor (FGF) 2 displayed an enhanced level of DCN expression, while LECs treated with transforming growth factor (TGF)β-2 showed a decrease in DCN expression. The expression of tropomyosin 1 (Tpm1), a marker of lens EMT increased after the addition of TGFβ-2 in human LEC; however, upregulation of Tpm1 mRNA or protein expression was reduced in human LECs overexpressing human DCN (hDCN). No phenotypic changes were observed in the lenses of 8- and 48-week-old transgenic mice for lens-specific hDCN (hDCN-Tg). Injury-induced EMT of the mouse lens, and the expression patterns of α smooth muscle actin, were attenuated in hDCN-Tg mice lenses. Overexpression of DCN inhibited the TGFβ-2-induced upregulation of Tpm1 and EMT observed during wound healing of the lens, but it did not affect mouse lens morphology until 48 weeks of age. Our findings demonstrate that DCN plays a significant role in regulating EMT formation of LECs and PCO, and suggest that for therapeutic intervention, maintenance of physiological expression of DCN is essential to attenuate EMT progression and PCO formation.

Original languageEnglish (US)
JournalCells
Volume10
Issue number4
DOIs
StatePublished - Apr 9 2021

Keywords

  • Decorin
  • epithelial-mesenchymal transition
  • lens development
  • posterior capsule opacification
  • wound healing

ASJC Scopus subject areas

  • Medicine(all)

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