Conjunctivitis is the major atopic disease affecting the ocular surface. Indeed, it is one of the most commonly observed diseases in ophthalmic clinics. Patients with the condition are hypersensitive to normally innocuous substances and suffer from symptoms ranging from mild itching and burning, to chemosis, conjunctival hyperemia, lid edema and at its worst, scarring of the ocular surface and permanent visual impairment. New therapeutic agents are desired due to the side affects of current medications, and the failure of these approaches in severe cases. The design of new drugs require a better understanding of the pathophysiology and biogenesis of the disease. Previous data indicate that while the pathophysiology of atopic conjunctivitis resembles that of rhinitis and asthma, there are also important variables that determine whether allergic inflammation will occur in each, or only a subset of these disparate sites in a particular individual. All data indicate that patients with allergic conjunctivitis share the same atopic condition with rhinitics and asthmatics. The patients with elevated serum gE levels, and the Th2 type cytokines are produced from both Tcells and degranulating mast cells and basophils in the conjunctival epithelium and stroma. However, a large portion of skin test positive individuals would only develop an allergic response in a specific mucosae. The PI hypothesizes that there are particular gene products that specifically target the allergic response to the eye in patients with conjunctivitis, just as they are thought to be specific asthma-predisposing genes. She and others have made significant progress in our efforts to identify potential """"""""atopy"""""""" associated markers as well as candidate atopic genes, and will systematically assess the contribution of each of those to atopic conjunctivitis in a large population of patients. Recent progress from her group is included in the preliminary data section of the grant. The first phase of linkage studies will focus on selected markers near (or within) candidate atopic genes. This will be followed by a genomic wide scan for novel determinants using microsatellite markers spaced evenly throughout the human gene map. The PI hopes that the identification of gene products involved in the pathogenesis of allergic conjunctivitis will permit the development of novel therapies for those afflicted with the disease and with other inflammatory diseases of the eye.
| Toda, Masako; Dawson, Maria; Nakamura, Takao et al. (2004) Impact of engagement of FcepsilonRI and CC chemokine receptor 1 on mast cell activation and motility. J Biol Chem 279:48443-8 |
| Nakamura, Takao; Toda, Masako; Ohbayashi, Masaharu et al. (2003) Detailed criteria for the assessment of clinical symptoms in a new murine model of severe allergic conjunctivitis. Cornea 22:S13-8 |
