Two diseases of humans are characterized by giant papillary conjunctivitis (GPC) of the upper lid: vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis. The long-term goal of this project is to produce animal models of these diseases that have the same clinical and histologic features as do the diseases in people. These eye diseases affect over one million Americans. Both have potentially blinding complications through damage to the cornea. A model of GPC should have the following features: (1) it should manifest an inflammatory reaction that is especially severe in the upper tarsal conjunctiva; (2) it should be characterized by basophil and eosinophil infiltration in the conjunctival epithelium and substantia propria; and (3) it should involve increased synthesis of collagen in the upper tarsal conjunctiva. To generate these models, we will induce (Aim 1) mucosal basophil hypersensitivity in the guinea pig by the injection of keyhole limpet hemocyanin into the upper tarsal conjunctiva. Clinical changes will be sought by slit lamp examination; histologic changes, consisting of basophil, eosinophil, and othe inflammatory cells, will be sought by light microscopy of sections. New collagen synthesis will be determined by measuring 14C-proline incorporation into hydroxyproline. The location of the newly synthesized collagen will be determined by 3H-proline autoradiography. We will induce (Aim 2) augmented anaphylaxis of the upper lid conjunctiva by injecting antigen into the site of a previously existing ocular mucosal basophil hypersensitivity reaction. This basophil-dependent anaphylaxis will be compared with mast cell anaphylaxis in conjunctivas of additional guinea pigs. We will also attempt (Aim 3) to induce ocular mucosal basophil hypersensitivity in the upper tarsal conjunctiva by topical application of antigen to the eye of a sensitized guinea pig. The role of contact lenses in enhancing the induction or severity of the disease will be evaluated. The synthesis of new collagen in the affected conjunctiva will be examined. We will explore (Aim $) whether both T-cells and antibody can cause ocular mucosal basophil reaction by transfer of lymphocytes or serum from immunized to naive animals. We will seek to determine (Aim 5) whether, upon transfer of lymphocytes from animals primed for classic delayed hypersensitivity reaction, we can uncover a mucosal basophil hypersensitiviy reaction in ocular tissues challenged with antigen.
| Hann, L E; Cornell-Bell, A H; Marten-Ellis, C et al. (1986) Conjunctival basophil hypersensitivity lesions in guinea pigs. Analysis of upper tarsal epithelium. Invest Ophthalmol Vis Sci 27:1255-60 |
