caa a22 4500 445292555 CHVBK 20180317142532.0 cr unu---uuuuu 170323e20100701xx s 000 0 eng 10.1007/s11626-010-9319-x doi (NATIONALLICENCE)springer-10.1007/s11626-010-9319-x Ciliary neurotrophic factor: a survival and differentiation inducer in human retinal progenitors [Elektronische Daten] [Kamla Dutt, Yang Cao, Ifeoma Ezeonu] Retinitis pigmentosa, age-related macular degeneration, and Parkinson's disease remain major problems in the field of medicine. Some of the strategies being explored for treatment include replacement of damaged tissue by transplantation of healthy tissues or progenitor cells and delivery of neurotrophins to rescue degenerating tissue. One of the neurotrophins with promise is the ciliary neurotrophic factor (CNTF). In this study, we report the role played by CNTF in retinal cell differentiation and survival in retinal progenitors. We found that CNTF is a survival factor for multipotential human retinal cells and increased cell survival by 50%, over a 7-d period, under serum-free conditions, as determined by apoptotic assays (immunohistochemistry and flow cytometry). This effect is dose dependent with a maximum survival at a CNTF concentration of 20ng/ml. We also report that CNTF might be a cell commitment factor, directing the differentiation mainly toward large multipolar cells with ganglionic and amacrine phenotype. These cells express tyrosine hydroxylase (amacrine cells) as well as, thy 1.1 and neuron-specific enolase (ganglionic cells). Additionally, there was also an increase in protein kinase C alpha, a protein expressed in rod and cone bipolars as well as cone photoreceptors and calbindin, a protein expressed in cone photoreceptors and horizontal cells. In our studies, CNTF doubled the number of cells with ganglionic phenotypes, and basic fibroblast growth factor doubled the number of cells with photoreceptor phenotype. Additionally, CNTF induced a subset of progenitors to undergo multiple rounds of cell division before acquiring the large multipolar ganglionic phenotype. Our conclusion is that CNTF could be an agent that has therapeutic potential and possibly induces differentiation of large multipolar ganglionic phenotype in a subset of progenitors. The Society for In Vitro Biology, 2010 Ciliary neurotrophic factor nationallicence Survival factor nationallicence Human retinal progenitors nationallicence Differentiation nationallicence Dutt Kamla Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., 30310-1495, Atlanta, GA, USA aut Cao Yang Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., 30310-1495, Atlanta, GA, USA aut Ezeonu Ifeoma Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., 30310-1495, Atlanta, GA, USA aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/7(2010-07-01), 635-646 1071-2690 46:7<635 2010 46 11626 https://doi.org/10.1007/s11626-010-9319-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11626-010-9319-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dutt Kamla Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., 30310-1495, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Cao Yang Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., 30310-1495, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Ezeonu Ifeoma Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., 30310-1495, Atlanta, GA, USA aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/7(2010-07-01), 635-646 1071-2690 46:7<635 2010 46 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer