keratan-sulfate and Eye-Injuries--Penetrating

Lens epithelial cells (LECs) undergo epithelial-mesenchcymal transition (EMT) after injury and transform into myofibroblasts positive for alpha-smooth muscle actin (alphaSMA), an established marker of this process. Lumican is a keratan sulfate proteoglycan core protein. This study was conducted to examine whether human and mouse LECs express lumican after injury. To determine whether lumican may modulate EMT of LECs in response to injury or to exposure to transforming growth factor-beta2 (TGFbeta2), alphaSMA expression by the LECs was examined in lumican (Lum)-knockout mice in vivo and in organ culture.. Human postoperative capsular specimens and healing, injured mouse lenses at various intervals were immunostained for lumican or alphaSMA. alphaSMA was also immunolocalized in healing, injured lenses of Lum-knockout mice. Finally, expression of lumican and alphaSMA was examined in lenses of Lum-knockout mice incubated with TGFbeta2.. Lumican was immunolocalized in matrix in human postoperative capsular opacification. Lumican and alphaSMA were upregulated in mouse LECs from 8 hours and day 5 after an injury, respectively. LECs accumulated adjacent to the capsular break were of epithelial shape in Lum(-/-) mice and fibroblast-like in Lum(+/-) mice during healing. alphaSMA expression by LECs was significantly delayed in Lum(-/-) mice, indicating that lumican may modulate injury-induced EMT in LECs. TGFbeta2-induced EMT appeared to be suppressed in organ-cultured lenses of Lum(-/-) mice compared with those of Lum(+/+) mice.. Human capsular opacification contains lumican, and mouse LECs upregulate lumican and alphaSMA in response to injury. Loss of lumican perturbs EMT of mouse LECs.

Topics: Actins; Adult; Aged; Aged, 80 and over; Animals; Cataract; Cataract Extraction; Chondroitin Sulfate Proteoglycans; Collagen Type I; Epithelial Cells; Eye Injuries, Penetrating; Female; Fibroblasts; Humans; Immunoenzyme Techniques; Keratan Sulfate; Lens Capsule, Crystalline; Lumican; Male; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Organ Culture Techniques; Postoperative Complications; Transforming Growth Factor beta; Transforming Growth Factor beta2; Up-Regulation; Wound Healing