title: Direct differentiation of adult ocular progenitors into striatal dopaminergic neurons.
abstract: Parkinson's disease, characterized by motor dysfunction due to the loss of nigrostriatal dopaminergic neurons, is one of the most prevalent age-related neurodegenerative disorders. Given there is no current cure, the stem cell approach has emerged as a viable therapeutic option to replace the dopaminergic neurons that are progressively lost to the disease. The success of the approach is likely to depend upon accessible, renewable, immune compatible, and non-tumorigenic sources of neural progenitors from which stable dopaminergic neurons can be generated efficaciously. Here, we demonstrate that neural progenitors derived from limbus, a regenerative and accessible ocular tissue, represent a safe source of dopaminergic neurons. When the limbus-derived neural progenitors were subjected to a well-established protocol of directed differentiation under the influence of Shh and FGF8, they acquired the biochemical and functional phenotype of dopaminergic neurons that included the ability to synthesize dopamine. Their intrastriatal transplantation in the rat model of hemi-Parkinsonism was associated with a reduction in the amphetamine-induced rotation. No tumor formation was observed 6 weeks post-transplantation. Together, these observations posit limbus-derived neural progenitors as an accessible and safe source of dopaminergic neurons for a potential autologous ex-vivo stem cell approach to Parkinson's disease.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Parameswaran
authors.affiliation: Department of Pharmacy Practice, Creighton University, Omaha, NE.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Destache
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodriguez-Sierra
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Hiba
authors.initials: H
authors.lastname: Ahmad
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: John
authors.initials: J
authors.lastname: Sorrentino
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Sudha
authors.initials: S
authors.lastname: Balasubramanian
keywords: Directed differentiation; Dopaminergic neurons; Parkinson’s disease; Stem cells