Thomas E. Gillette

Langerhans Cells of the Ocular Surface

Recent evidence has been collected by several investigators defining a distinct population of dendritic cells (Langerhans cells) of mesenchymal origin residing in the epidermal surfaces of many mammalian species. These cells play a dominant role in the processing of antigens presented through cutaneous surfaces and carry a Class II histocompatability antigen felt to be of central importance in the afferent arm of allograft rejection. They also possess many of the characteristics of macrophages active in the efferent arm of immunologic responses. An equivalent subset of dendritic cells (Langerhans cells) in ocular surface epithelium of the human, mouse rat, and guinea pig has been identified by enzyme histochemistry, immunofluorescence, and electron microscopy. Ocular surface Langerhans cells proliferate in the setting of corneal inflammation (remote and recent) and are depleted by topical and systemic corticosteroids. Ocular surface Langerhans cells may play a central role in ocular contact hypersensitivity, corneal allograft rejection, and ocular surface immune surveillance.

Immunologic Defense Mechanisms of the Ocular Surface

The ocular surface represents an immunologic microcosm in which certain local immunologic and paraimmunologic defense systems analogous or identical to those of other mucosal surfaces are operative. These defenses include a resident normal flora; intrinsic anatomic barriers; secretion of mucous and certain chemical bacteriostatics and bacteriolytics; local humoral (slgA) antibody secretion; and local T-lymphocyte cellular responses. A series of sophisticated mechanisms has evolved to defend the ocular surface against diverse environmental pathogens. Often, the activation of one system leads to the subsequent activation of another, providing a highly integrated, series of mechanisms for host defense. And, it is clear that close integration of these various mechanisms provides a highly efficient amplification system for host defense, so that when one mechanism fails to deal with the invading pathogen the next mechanism is then efficiently initiated. Only in those situations where the pathogen overwhelms these defense systems, or is of such a persistent nature that it becomes resistant to removal by these various mechanisms, or alternatively is able to subvert its identity and, therefore, evade these mechanisms do organisms infect and cause disease. It is undoubtedly the complex interaction of all of these defense systems, both paraimmunologic and immunologic, which finally determines the integrity of the ocular surface.

Histologic and immunohistologic comparison of main and accessory lacrimal tissue.

Main and accessory lacrimal tissues from autopsy and biopsy specimens were compared histologically and immunohistologically. Formaldehyde-fixed, paraffin-embedded specimens were studied by light microscopy with hematoxylinand-eosin and PAS staining. Glutaraldehyde-fixed, Epon-embedded specimens were sectioned at 1 micron, stained with alkaline Giemsa, and studied by light microscopy. Specimens fixed in a solution of alcohol and acetic acid were stained by immunofluorescence techniques for lactoferrin, lysozyme, secretory component, and the immunoglobulins IgG, IgA, IgM, IgD, and IgE. The main and the accessory lacrimal tissues were identical histologically and had identical distributions of secretory products and immunoglobulin-containing plasma cells. The finding of myoepithelial cells in 1-micron sections of accessory lacrimal tissue indicates autonomic innervation in that tissue. This finding, in conjunction with the identical immunohistology, indicates a common source for unstimulated and stimulated tears.

Recurrent Keratoconus After Keratoplasty

A 35-year-old woman who had undergone bilateral penetrating corneal grafts for keratoconus had keratoconus in the eye that had received a graft 16 years earlier. A second penetrating keratoplasty was performed, and the excised button was examined with light and electron microscopy. Both the light and electron microscopic findings were consistent with the clinical diagnosis of keratoconus. Keratoconus in a graft for the same disease should be added to the list of late complications of successful keratoplasties.

Immunofluorescence and histochemistry of corneal epithelial flat mounts: Use of EDTA

We describe a simple and reliable technique for the preparation of corneal epithelial flat mounts. The technique is based on incubation of corneas or whole globes in an EDTA solution prior to fixation. Corneal epithelial flat mounts prepared by this technique are suitable for study by immunofluorescence or enzyme histochemistry.

Experimental corneal allograft rejection: Description of murine model and a new hypothesis of immunopathogenesis

A murine model of heterotopic corneal transplantation has been developed. Whole corneas were removed from either inbred Balb/cJ or C57B1/6J mice and inserted into an abdominal subcutaneous pouch in C57B1/6J recipient mice. Fresh donor tissue, donor corneas cultured at 37°C in 5 per cent CO2-95 per cent room air, or donor corneas cultured at 37°C in two atmospheres of 98 per cent 02 - 2 per cent CO2 (hyperbaric oxygen) were utilized. Twenty-one days later, the recipients were sacrificed and the heterotopic grafts were examined in a masked fashion. Rejected grafts were edematous, opaque, and vascularized. In contast, unrejected grafts were clear and nonvascularized. These results were further confirmed by histological examination of the donor grafts in a masked fashion. Control syngeneic grafts were not rejected. The fresh allografts were usually rejected (91%) as were the allografts cultured in CO2 - room air (90%). Thus, this murine model of heterotopic corneal transplantation appears to be useful for the...