Researchers in the Saghizadeh Ghiam Laboratory study the microRNA regulatory mechanisms of limbal epithelial stem cell (LESC) proliferation, migration, adhesion and differentiation in normal cornea homeostasis and wound-healing processes. Understanding these mechanisms could be key to understanding corneal diseases.
Treating Corneal Diseases
A wide variety of physiological and pathological conditions, such as infections, inflammations and corneal diseases including limbal stem cell deficiency (LSCD) and diabetes can affect LESC functions, resulting in serious vision problems. Altered wound-healing processes, as seen in diabetic cornea, can result in corneal vascularization and loss of transparency, leading to corneal blindness. Currently, there is a need to better understand the mechanisms responsible for these abnormalities and develop new and efficacious treatments. The mechanisms of LESC proliferation, migration, adhesion and differentiation in normal corneal homeostasis and wound healing could be key to managing corneal diseases. Therefore, the understanding of miRNA regulatory mechanisms is critically important in the etiology and treatment of various corneal diseases such as LSCD and diabetic keratopathy, which are the major causes for corneal blindness.
Understanding the Role of MicroRNAs
The Saghizadeh Ghiam Laboratory employs a variety of molecular, functional tests and ex vivo human organ-cultured corneas to understand the role of microRNAs in both differentiated epithelial and stem cells of normal and diabetic corneas and their roles in driving LESC activation in normal and diseased cornea. The focus of the Saghizadeh Ghiam Lab is determining the targets of microRNAs, and attempting gene therapy with either overexpression or silencing of specific microRNAs to normalize corneal wound healing and LESC marker patterns in diabetic cornea. We target diabetic corneal epithelial cells by single microRNA, or their combinations, to improve function of corneal epithelium. This research could lead to the generation of a new cell source for restoring vision in patients with altered LESC.
Our lab has identified several miRNAs with altered expression in diabetic corneas using gene array, which correlates with their effects on corneal cell wound healing. We have also performed deep sequencing analysis of a large group of human normal and diabetic corneas resulting in the identification of promising miRNA candidates for further analysis. These studies may lead to restoration of normal functions to diabetic corneal stem cells. We were able to successfully treat delayed wound healing in human diabetic organ-cultured corneas by targeting miR-146a in human diabetic organ-cultured corneas.