Limbal Stem Cell Deficiency (LSCD) is characterized by ocular pain, poor re-epithelialization, corneal ulceration, conjunctival cell ingrowth and loss f visual acuity. LSCD may be secondary to myriad conditions such as Steven Johnson's Syndrome, ocular cicatricial pemphigoid, chronic inflammation and chemical injury. Transplantation of corneal epithelial stem cells to stem cell deficient corneas has the potential t restore sight to blind eyes. Improving the rehabilitation of patients with stem cell deficiency wil require the ability to better harness and induce the regenerative capacity of adult corneal epithelial stem cells. The proposed research will capitalize upon the slow cycling phenotype of stem cells to aid in identifying, purifying and expanding corneal stem epithelial cell populations using a murine transgenic pulse-chase system.
Aim 1 will characterize the gene expression profile of slow cycling cells in the murine cornea. The system will be optimized in subaim 1.1 and isolated slow cycling cells will undergo gene expression analysis in subaim 1.2.
Aim 2 will use in vitro and in vivo models to evaluate the regenerative potential of slow cycling corneal epithelial cells. Finally, Aim 3 will identify slow cycling cell related genes that are critical fo corneal epithelium regeneration.
Damage to the ocular surface is a common endpoint for an array of corneal conditions including trauma, infection, and inflammation. This damage may cause loss of corneal epithelial stem cells and result in persistent epithelial defects, or encroachment of con-corneal epithelium onto the ocular surface with concomitant risk of corneal ulceration and loss of vision. Our work will characterize the stem cells in a novel way, which could lead to new therapies for corneal epithelial stem cell deficiency.
Sartaj, R; Zhang, C; Wan, P et al. (2017) Characterization of slow cycling corneal limbal epithelial cells identifies putative stem cell markers. Sci Rep 7:3793 |
Sartaj, Rachel; Chee, Ru-ik; Yang, Jing et al. (2016) LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis. Stem Cells 34:493-503 |