The corneal epithelium is one of the most sensitive and critical structures of the eye. It is affected in nearly every disease of the ocular surface, ranging from corneal abrasions and dry eyes to severe corneal melts and infections. Currently, there are very limited treatments that can specifically enhance the corneal epithelial function. In particular, there are no pharmacologic approaches to promote epithelial repair in patients with a compromised corneal epithelial barrier. The long term objective of this research application is to contribute to the development of novel and innovative treatments for patients with visually disabling ocular surface diseases by defining the mechanisms of epithelial barrier disease and repair. Our preliminary studies provide strong evidence that Notch1 plays a key role in regulating the corneal epithelial barrier repair and thus Notch1-/- mice provide a unique model for studying corneal epithelial barrier disease. To accomplish the research objectives of this application, the following two specific aims will be pursued: (1) Characterize the epithelial barrir function and the cell-cell adhesion defect using mice with conditional loss of Notch1 as a model, (2) Elucidate the inflammatory signaling pathways that are activated during epithelial injury/repair and determine their role in the development of inflammation and metaplasia using Notch1-/- mice as a model. These results will provide critical information for the development of therapies for patients with visually disabling ocular surface disorders. We will identify a number of candidate pathways and drugs for clinically enhancing the function of the corneal epithelium and suppressing corneal inflammation.
A clear cornea is essential for normal vision. The most superficial layer of the cornea, known as the epithelium, is affected in many disorders that result in severe visual impairment. This project aims to find new treatments that will enhance the function of the corneal epithelium, particularly ways to improve its integrity and protective function.
| Eslani, Medi; Putra, Ilham; Shen, Xiang et al. (2018) Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage Immunophenotype and Angiogenic Function. Stem Cells 36:775-784 |
| Roshandel, Danial; Eslani, Medi; Baradaran-Rafii, Alireza et al. (2018) Current and emerging therapies for corneal neovascularization. Ocul Surf 16:398-414 |
| Rouhbakhshzaeri, Majid; Rabiee, Behnam; Azar, Nathalie et al. (2018) New ex vivo model of corneal endothelial phacoemulsification injury and rescue therapy with mesenchymal stromal cell secretome. J Cataract Refract Surg : |
| Samaeekia, Ravand; Rabiee, Behnam; Putra, Ilham et al. (2018) Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing. Invest Ophthalmol Vis Sci 59:5194-5200 |
| Ghaffari, Reza; Ghassemi, Hamed; Zarei-Ghanavati, Mehran et al. (2017) Tacrolimus Eye Drops as Adjunct Therapy in Severe Corneal Endothelial Rejection Refractory to Corticosteroids. Cornea 36:1195-1199 |
| Yazdanpanah, Ghasem; Jabbehdari, Sayena; Djalilian, Ali R (2017) Limbal and corneal epithelial homeostasis. Curr Opin Ophthalmol 28:348-354 |
| Baradaran-Rafii, Alireza; Eslani, Medi; Haq, Zeeshan et al. (2017) Current and Upcoming Therapies for Ocular Surface Chemical Injuries. Ocul Surf 15:48-64 |
| Thulasi, Praneetha; Djalilian, Ali Reza (2017) Update in Current Diagnostics and Therapeutics of Dry Eye Disease. Ophthalmology 124:S27-S33 |
| Eslani, Medi; Putra, Ilham; Shen, Xiang et al. (2017) Corneal Mesenchymal Stromal Cells Are Directly Antiangiogenic via PEDF and sFLT-1. Invest Ophthalmol Vis Sci 58:5507-5517 |
| Jabbehdari, Sayena; Rafii, Alireza Baradaran; Yazdanpanah, Ghasem et al. (2017) Update on the Management of High-Risk Penetrating Keratoplasty. Curr Ophthalmol Rep 5:38-48 |
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