Mice lacking syndecan-1 are viable, fertile and have morphologically normal skin, hair and ocular surface epithelia. While studying the response of these mice to corneal epithelial and skin wounding, we identified defects in epithelial cell proliferation and regulation of integrin expression. mRNA profiling of corneal epithelial tissues obtained from wild-type and syndecan-1-/- mice suggest that these defects result from differences in overall gene transcription. In the cornea,syndecan-1-/- epithelial cells migrate more slowly, show reduced localization of α9 integrin during closure of wounds and fail to increase their proliferation rate 24 hours after wounding. In the skin, we did not document a migration defect after full thickness wounds but did observe cell proliferation delays and reduced localization of α9 integrin in the syndecan-1-/- epidermis after dermabrasion. Despite increased cell proliferation rates in the uninjured syndecan-1-/- epidermis and the corneal epithelium, morphologically normal epithelial thickness is maintained prior to injury; however, wounding is accompanied by prolonged hypoplasia in both tissues. Analyses of integrin protein levels in extracts from full thickness skin, revealed increased levels of α3 and α9 integrins both prior to injury and after hair removal in syndecan-1-/- mice but no increase 2 days after dermabrasion. These data for the first time show involvement of α9 integrin in skin wound healing and demonstrate essential roles for syndecan-1 in mediating cell proliferation and regulation of integrin expression in normal and wounded epithelial tissues.
The strength of the electric fields in the vicinity of 1.5 mm circular lesions in the bovine cornea has been found to influence the rate of re-epithelization. A decrease in the field strength by submersion of the lesions or by treating the lesions with the Na+-channel blocker, benzamil, significantly retarded healing. An increase in the field strength of lesions treated with Na+-depleted Hanks' solution, by the addition of direct current, increased epithelization. Epithelization was fastest in wounds with field strengths raised to - 80 mV/mm, more than twice the normal field strength present in wounds maintained in Hanks' solution alone. Epithelization decreased, however, when the field strengths were increased to -120 mV/mm. A similar pattern was also observed when the field's polarity was reversed. By manipulating and monitoring the field strengths, we have been able to show for the first time that increased wound field strengths enhance corneal wound epithelization, and that field strengths with reversed polarity also enhance this epithelization.
Progenitor cells from adult mammalian ciliary body have significant, but limited, proliferation potential and express markers characteristic of other progenitor cells and seen during early retinal development. The ciliary body could be a source of cells for transplantation in experimental rodent eyes and for autotransplantation in human eyes.
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