""""""""Blepharitis"""""""" is probably the most common non-refractive clinical problem confronting the general ophthalmologist in practice. Meibomian gland dysfunction (MGD) is one subset of chronic blepharitis. We have developed two relevant models of MGD/blepharitis in rabbits. One (hyperkeratinization) is partially studied and the other (meibomian gland atrophy) has been subjected only to pilot studies. Our research team, including a clinician, an experimental pathologist, a lipid biochemist, and an immunochemist propose to study the pathogenesis of MGD in these two models. The models will then be used to develop treatment strategies applicable to man. We will test two hypotheses related to these models: Hypothesis 1: Alterations in meibomian gland ductal epithelial cell keratin protein expression leads to hyperkeratinization, obstruction of the duct and MGD with secondary clinical features related to ocular surface and tear film changes. Hypothesis 2: Maturation of meibomian gland acinar cells from undifferentiated basal cells to mature differentiated acinar cells is inhibited or delayed leading to gland atrophy, MGD and clinical features related to ocular surface and tear film changes. Our topical epinephrine rabbit model will be used to test Hypothesis 1; the 13-cis retinoic acid rabbit model will be used to test Hypothesis 2. Experimental procedures which will be utilized to study these models include extensive morphologic studies (light microscopy, SEM, and TEM) of the meibomian gland acini, ducts, lid margins and orifices; immunofluorescent and biochemical techniques to assess keratin proteins or epithelial cells in the meibomian gland, microbiologic studies of microbial flora and microanalytic biochemical techniques to assess lipid constituents of meibomian gland excreta. Objective clinical changes in meibomian gland dysfunction, including transillumination infrared biomicroscopy of the meibomian glands in vivo will also be done. Clinical trials of various therapies are planned for later years of the grant application, including possible study of tetracycline, Vitamin A derivatives, etc. Effects of MGD on tear film parameters (osmolarity), the conjunctival and corneal epithelium (impression cytology, goblet cell density) and the lid margin will also be assessed.
