The corneal endothelium of man possesses essentially no regenerative capabilities; typically, in vivo cell loss is followed by compensatory hypertrophy of the remaining endothelium. This lack of regenerative capacity poses a significant clinical problem as many corneal diseases are accompanied by substantial endothelial cell loss, eventually resulting in irreversible corneal edema. Presently, clinical replacement of the corneal endothelium is achieved by homotransplantation of healthy donor corneas. Conventional replacement therapy, however, has placed moderate limitations on the quality and number of donor corneas presently suitable for keratoplasty. With the eventual goal of increasing the potential pool of donor corneas available for transplantation purposes, we propose a set of experiments designed to augment/enhance existing donor corneas. These studies are supplemental to our ongoing studies of endothelial seeding (where there is complete replacement of the donor endothelial monolayer) and are designed to increase the endothelial cell densities of normal (suitable) tissue and low density corneas which otherwise would not be suitable for penetrating keratoplasty. In addition to the potential for increasing the supply of tissue by improving the quality of low density donor corneas, any increase in the cell density of the endothelial monolayer will provide greater endothelial reserve following penetrating keratoplasty. Endothelial cell loss following penetrating keratoplasty shows a significant one year cell loss of 33-45%. This leaves very little endothelial reserve for future demands on the traumatized endothelium following penetrating keratoplasty. Our proposed experiments involving the addition of EGF and/or FGF to cell suspensions, and augmentation of existing monolayers with exogenous cells are all designed to Increase the endothelial cell density of corneas prior to corneal transplantation. The potential human applications of these results have far reaching clinical implications. The replacement of a damaged (diseased) endothelium with a viable cell cultured endothelium (establish human cryopreserved corneal endothelial cell banks) to repopulate aging or diseased corneas prior to, during, or in place of penetrating keratoplasty would dramatically increase the number of corneas suitable for transplantation, provide a means of standardizing the established population of donor preparations and increase the safety and success of future human corneal transplant surgery.
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