The purpose of this research is to identify and characterize the cellular processes of corneal wound healing which determine wound contraction and modification of corneal curvature. Previous studies suggest that modification of corneal curvature by surgical incisions, ie radial keratotomy (RK), relaxing incisions and Ruiz procedures, may be determined by post surgical wound gape. Our preliminary results indicate however, that during subsequent corneal wound healing, activated fibroblasts develop controactile properties, similar to skin myofibroblasts, which may reduce initial wound gape and cause short and long term changes in corneal curvature. Understanding the critical relationships between the cellular events of corneal wound healing, wound gape and corneal curvature is thus fundamental to any clinical predictability of the effects of refractive surgical procedures. Proposed experiments will: (1) Establish the natural history in vivo of quantitative changes in total corneal shape following RK in cats and primates by computerized keratography: (2) Correlate changes in corneal shape with in vivo quantitative measurements of wound gape, size, depth, length and orientation using Tandem Scanning Reflected Light Microscopy (TSRLM); (3) Establish definitive in vivo TSRLM-identified cellular responses associated with corneal wound healing following RK including: keratocytes, activated fibroblasts, endothelium, epithelium, and inflammatory cells; (4) Correlate in vivo TSRLM observations of the cellular responses of wound healing with the morphologic changes in the same eye by light, scanning and transmission EM; (5) Establish the biologic response over time of corneal healing following RK by: (a) immunocytochemistry; (b) quantitative biochemical analysis; and (c) measuring in vitro wound contractility; (6) Correlate the biologic response including contractile properties to established concurrent changes in corneal curvature and wound gape, size, depth, length and orientation measured by TSRLM and computerized keratography; (7) Characterize the acute and chronic effects of substances known to modulate wound healing, such as topical corticosteroids, bisamino propriononitril and epidermal growth factor on corneal curvature and on the biological response of wound healing.
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