Friday October 26th 10am-12 Noon
Room 122 A-C
Christina S. Wilmer, OD, FAAO
Professor and Dean of Optometry, Indiana University, Bloomington
Why are topical CAIs contraindicated in corneas with low endothelial cell count?
The corneal endothelium is responsible for maintaining the hydration and transparency of the cornea. Trauma, inflammation, or dystrophies (e.g. Fuchs dystrophy) can reduce endothelial function leading to corneal edema and loss of vision. The endothelial “pump” has been described as a bicarbonate and carbonic anhydrase dependent ion secretory mechanism that creates osmotic gradients leading to water efflux that exactly counterbalances water influx driven by stromal glycosaminoglycans. We now present evidence indicating that bicarbonate and carbonic anhydrase activity act to buffer corneal lactic acid transport across the endothelium and that this facilitation of lactate transport is a significant contributor to the endothelial pump. These new insights also provide a context for the role of carbonic anhydrases and an explanation for reports of corneal decompensation in patients using topical carbonic anhydrase inhibitors.
Despite a plethora of new products, the incidence of contact lens related infection has not changed since soft lenses were first introduced onto the market about 40 years ago. It is becoming increasingly clear that basic research to understand the mechanisms cannot be circumvented if the problem is ever to be solved. In recent years, our laboratory has capitalized on new technologies and an explosion of information in the field of molecular and cellular biology to develop various new models and methods. These are now providing answers to long standing questions about to how the healthy cornea resists infection, how contact lens wear compromises that resistance, and how microbes take advantage of that to cause disease. Data arising from these experiments is informing us about how lens wear could be made safer, and suggest exciting and novel strategies for managing infection whatever the cause.
Mechanisms of corneal epithelial maintenance: understanding the effects of systemic disease and contact lens wear
The corneal epithelium is a self-renewing stratified epithelial sheet that provides a barrier against invading pathogens and a smooth refracting surface essential for vision. A coordinated balance between proliferation, differentiation and apoptotic desquamation coupled with dynamic regulation of intercellular junction formation contributes to homeostatic tissue maintenance as cells divide, migrate and shed throughout the course of normal cellular turnover. Using contemporary imaging, molecular and biochemical techniques, we are investigating fundamental gene regulatory mechanisms and protein-protein interactions that regulate normal corneal epithelial homeostatic renewal and are disrupted by injury or disease. To accomplish this, we have implemented two clinically relevant models that perturb normal epithelial homeostatic renewal: hyperglycemic-induced corneal epithelial changes as seen in diabetic disease; and contact lens wear, where mechanical and chemical effects from lenses and/or solutions alter both renewal and barrier function properties, predisposing the cornea to infection.