Paracrine Effects of Keratocytes, Limbal Mesenchymal Stem Cells, and Myofibroblasts on Corneal Fibroblasts

To study corneal homeostasis, corneal fibroblasts were cultured for 24 and 72 h on a corneal lens in the presence of conditioned media from cells of healthy cornea (keratocytes and limbal MSCs) or fibrous cornea (myofibroblasts). Conditioned media from keratocytes and limbal MSCs induced changes in fibroblast morphology, increased cell necrosis throughout the observation period (72 h), reduced proliferative activity and the number of CXCR4⁺ corneal fibroblasts, and induced opposite shifts in the level of SDF-1 secretion. The conditioned medium of myofibroblasts increased the number of Ki-67⁺ and CXCR4⁺ fibroblasts after 24 h and cell apoptosis after 72 observations; it also decreased SDF-1 production by fibroblasts. Our data demonstrate that regulation of CXCR4 receptor expression on corneal fibroblasts by the total soluble secretome plays an important role in maintaining corneal homeostasis.