Zeljka Smit-McBride, PhD – Ophthalmology and Vision Science

Dysregulation of MicroRNAs in Ocular Tissue Exposed to Cigarette Smoke

Age-related macular degeneration (AMD), a blinding disease having both genetic and environmental components, is the most common form of visual impairment in elderly individuals of the Western world, and smoking is the leading identified associated environmental insult. Recently, a central regulatory role for a novel type of molecule, microRNA (miRNA), had been discovered in many human diseases. MiRNAs are considered to be master regulatory switches, playing roles in stem cell differentiation, aging, epigenetics, etc. Although knowledge about miRNAs and their functions is rapidly accumulating, their roles in healthy ocular aging vs. age-related pathologies in the eye is lacking. Our long-term goal is to elucidate the regulatory role of miRNAs in the eye during normal aging and disease. The goal of this project is to address how circulatory miRNA populations change during normal eye aging, and how that process is accelerated and dysregulated during heightened level of environmental insult such as chronic exposure to cigarette smoke. Our central hypothesis is that normal age-related homeostatic processes whose failure causes/allows the transition from healthy aging to disease are regulated by miRNAs. We will determine which miRNAs show aging-related change of expression using a primate model, and then determine which miRNAs show environmental insult-related changes of expression using a primate model and chronic exposure to cigarette smoke. Identification of eye-specific miRNA will allow identification of novel strategies for intervention for blinding ocular diseases.