The corneal epithelium is one of the most sensitive and critical structures of the eye. Currently, the pathways that regulate the differentiation and renewal of the corneal epithelial cells are largely unknown. Understanding the precise regulatory pathways governing corneal epithelial regeneration is critical for the development of effective treatments for many corneal wound healing disorders. Notch signaling, which is an important pathway in cell-fate determination, has recently been implicated in corneal epithelial growth and differentiation. The long-term objective of this application is two fold. First, is to contribute to the development of novel and innovative treatments for patients with ocular surface disease by defining the role of Notch signaling in the regulation of corneal epithelial growth and differentiation. Second, is to further develop the career of the applicant as a clinician-scientist and facilitate his transition to becoming an independent investigator. To accomplish the research objectives of this application, the following three specific aims will be pursued: (1) Determine the expression of Notch receptors and ligands in the corneal epithelial cells during proliferation and differentiation. (2) Characterize the effects of induced Notch activation and inhibition on the growth and differentiation of the human corneal epithelial cells. (3) Determine the in vivo effects of Notch activation and inhibition in the murine corneal epithelium. In addition to pursuing these specific aims, the applicant will follow a carefully designed career development plan involving didactic and hands-on training under the direct supervision of experienced mentors. Overall, these studies will improve our understanding of how the surface of the eye is regenerated. These results will lead to the development of new treatments for patients with disabling visual conditions involving the surface of the eye.
| Kim, Bryan Y; Riaz, Kamran M; Bakhtiari, Pejman et al. (2014) Medically reversible limbal stem cell disease: clinical features and management strategies. Ophthalmology 121:2053-8 |
| Eslani, Medi; Movahedan, Asadolah; Afsharkhamseh, Neda et al. (2014) The role of toll-like receptor 4 in corneal epithelial wound healing. Invest Ophthalmol Vis Sci 55:6108-15 |
| Movahedan, Asadolah; Afsharkhamseh, Neda; Sagha, Hossein M et al. (2013) Loss of Notch1 disrupts the barrier repair in the corneal epithelium. PLoS One 8:e69113 |
| Milani, Behrad Y; Milani, Farnoud Y; Park, Dong-Wouk et al. (2013) Rapamycin inhibits the production of myofibroblasts and reduces corneal scarring after photorefractive keratectomy. Invest Ophthalmol Vis Sci 54:7424-30 |
| Choi, Daniel S; Djalilian, Ali (2013) Oral azithromycin combined with topical anti-inflammatory agents in the treatment of blepharokeratoconjunctivitis in children. J AAPOS 17:112-3 |
| Milani, Behrad Y; Majdi, Mercede; Green, Wesley et al. (2013) The use of peer optic nerve photographs for teaching direct ophthalmoscopy. Ophthalmology 120:761-5 |
| Shafiq, Maryam A; Gemeinhart, Richard A; Yue, Beatrice Y J T et al. (2012) Decellularized human cornea for reconstructing the corneal epithelium and anterior stroma. Tissue Eng Part C Methods 18:340-8 |
| Movahedan, Asadolah; Majdi, Mercede; Afsharkhamseh, Neda et al. (2012) Notch inhibition during corneal epithelial wound healing promotes migration. Invest Ophthalmol Vis Sci 53:7476-83 |
| Amirjamshidi, H; Milani, B Y; Sagha, H M et al. (2011) Limbal fibroblast conditioned media: a non-invasive treatment for limbal stem cell deficiency. Mol Vis 17:658-66 |
| Djalilian, A R; Namavari, A; Ito, A et al. (2008) Down-regulation of Notch signaling during corneal epithelial proliferation. Mol Vis 14:1041-9 |
