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G.B. Grunwald, S.J. Tate; Vitreous Treatment Induces Altered Cell Migration and Cadherin Subtype Expression During Retinal Pigment Epithelial Wound Healing in Organotypic Cultures . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2965.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Maintenance of an intact and normally differentiated retinal pigment epithelium (RPE) is critical to proper retinal function. Following injury due to trauma or surgery, the RPE is capable of wound healing. However, under some circumstances the normal course of RPE wound healing can be disrupted, which may lead to proliferative vitreoretinopathy (PVR). This may be due to altered RPE cell behavior, including increased cell proliferation and aberrant differentiation, resulting from exposure to vitreous following rhegmatogenous retinal detachment. To explore the underlying mechanisms, including altered RPE cell adhesion and signaling responses, we utilized an in vitro RPE organ culture system to determine the effects of vitreous exposure on RPE wound healing and associated changes in cadherin cell adhesion molecule expression. Methods: Explants consisting of intact RPE/Bruch's membrane/choroid were obtained by dissection from day 11-13 chick embryos, maintained in organ culture in vitro, wounded by partial debridement of the RPE cell layer, and examined for cadherin expression by immunocytochemistry following various periods of culture. Results: RPE cells maintained as intact, unwounded explant cultures retained a high level of R-cadherin and low level of N-cadherin, a ratio typical of mature RPE cells. Wounding and subsequent healing of the RPE monolayer was initially accompanied by reciprocal down-regulation of R-cadherin and up-regulation of N-cadherin among cells migrating into the wound, with the mature cadherin subtype ratio later restored as a confluent monolayer of well differentiated cells became re-established. However, exposure to vitreous during the wound healing phase resulted in altered healing of the wounded area, such that RPE cells, despite more rapidly migrating to fill in the wound, maintained a disorganized morphology and a high N-cadherin/low R-cadherin ratio typical of immature RPE cells. A sharp border between well differentiated and poorly differentiated RPE cells, with concommitant alteration of cadherin subtype expression ratios, was maintained around the original perimeter of the wound, indicating that the effect of vitreous on altered cadherin subtype expression only occurs among cells undergoing the wound healing response. Conclusions: These results suggest that the aberrant RPE cell behavior and wound healing that can occur following injury to the RPE in PVR may in part be due to altered cadherin expression resulting from vitreous exposure. This work was supported by NIH Grant RO1EY06658 to G.B.G.
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