CELL BIOLOGY OF THE OCULAR SURFACE DISEASES

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The ocular surface diseases, including ocular cicatricial pemphigoid (0CP), atopic keratoconjunctivitis (AKC), and Stevens-Johnson syndrome (SJS) are bilateral, progressive, blinding ocular diseases. The clinical findings of conjunctival scarring, Ed adhesions, tear deficiency and corneal opacification are responsible for the loss of vision. A similar clinical appearance characterizes healing of alkali or other chemical injuries. During the past 15 years, we have studied the epithelial changes in the conjunctiva and the cornea in these conditions, with particular emphasis on the mitotic rate (elevated) and the goblet cell frequency (variable). The scar formation found in these diseases involves the subepithelial tissue. This proposal addresses our change in focus from the epithelium to the subepithelial tissue, and to the fibroblasts themselves. Three specific aims are designed to explore the cell biology of the subepithelial fibroblasts in these conditions: I. Descriptive, baseline studies in rabbits to determine the role of the subepithelial fibroblasts in conjunctival healing after alkali injury; II. To study, on tissues from patients with various ocular surface diseases, the role of the subepithelial fibroblasts in conjunctival scarring; and III. To study the role of systemic immunosuppression on the biological characteristics of the epithelium and the subepithelial fibroblasts. Methods to be employed include morphology of conjunctival biopsies, immunostaining of fibroblasts to determine activation and collagen III production, and tissue culture behavior of fibroblasts. These features will be studied in alkali-burned rabbits and in treated and untreated patients, to determine the relationship between the characteristics of the fibroblasts and the clinical disease activity.