The candidate is an MD/PhD trained ophthalmologist and ophthalmic plastic surgeon with the career goal of studying stem cells and their application to cure ocular and orbital disease. The career development plan will be jointly mentored by Drs. Ihor Lemishcka and Mario Wolosin. Their laboratories focus of human embryonic and induced pluripotent stem cell biology and corneal limbal stem cells, respectively. The candidate's long-term aim is to understand what controls stem cell differentiation into distinct ocular and orbital tissues, with the goal of creating autologous tissue for transplantation. Over 6 million people worldwide are blind from damage to the ocular surface. Burns, trauma, infection, genetic diseases, and chronic inflammation result in limbal epithelial stem cell deficiency (LSCD) and persistent vision loss from corneal scarring, vascularization and conjunctivalization. Replacement of limbal stem cells is often required to restore vision. In unilateral LSCD cases, the fellow eye is an obvious autologous cell source;in patients with bilateral LSCD (in cases of bilateral blindness) limbal allografts are the only option. For reasons not fully understood, allografts often fail within a few years in these patients despite immunosuppression. Thus, autologous cells are necessary to restore lasting vision. We propose to develop a protocol to generate autologous induced pluripotent stem cell (iPSC)-derived cells capable of acquiring the corneal phenotype in vivo.
Our aims are to (1) generate iPSC from cells whose embryological origin is closer to the limbal- corneal lineage, which includes human eyelid skin, and conjunctival and buccal epithelia, (2) differentiate iPSC via progenitor cells using an ectodermal differentiation protocol in combination with soluble factors and limbal niche culture, and (3) assess the ability of the generated cells for ocular surface regeneration using an established human tissue into rabbit model. The funding for this proposal will facilitate the discovery of new stem cell therapies for ocular surface disease and make regenerative medicine a reality for those burdened with blindness.

Public Health Relevance

Over 6 million people worldwide are blind from damage to the ocular surface, yet treatments for bilateral blindness are extremely limited. This proposal outlines research to understand what controls differentiation of ocular surface stem cells and tries to develop new methods of creating safe, non-immunogenic tissue sources for transplantation, which will serve to improve vision.

National Institute of Health (NIH)
National Eye Institute (NEI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZEY1)
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Agarwal, Neeraj
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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Selver, Ozlem Barut; Durak, Ismet; G├╝rdal, Mehmet et al. (2016) Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants. Mol Vis 22:138-49