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Continuous Non-Cell Autonomous Reprogramming to Generate Retinal Ganglion Cells for Glaucomatous Neuropathy
- Source :
- Stem Cells. 33:1743-1758
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Glaucoma, where the retinal ganglion cells (RGCs) carrying the visual signals from the retina to the visual centers in the brain are progressively lost, is the most common cause of irreversible blindness. The management approaches, whether surgical, pharmacological, or neuroprotective do not reverse the degenerative changes. The stem cell approach to replace dead RGCs is a viable option but currently faces several barriers, such as the lack of a renewable, safe, and ethical source of RGCs that are functional and could establish contacts with bona fide targets. To address these barriers, we have derived RGCs from the easily accessible adult limbal cells, reprogrammed to pluripotency by a non-nucleic acid approach, thus circumventing the risk of insertional mutagenesis. The generation of RGCs from the induced pluripotent stem (iPS) cells, also accomplished non-cell autonomously, recapitulated the developmental mechanism, ensuring the predictability and stability of the acquired phenotype, comparable to that of native RGCs at biochemical, molecular, and functional levels. More importantly, the induced RGCs expressed axonal guidance molecules and demonstrated the potential to establish contacts with specific targets. Furthermore, when transplanted in the rat model of ocular hypertension, these cells incorporated into the host RGC layer and expressed RGC-specific markers. Transplantation of these cells in immune-deficient mice did not produce tumors. Together, our results posit retinal progenitors generated from non-nucleic acid-derived iPS cells as a safe and robust source of RGCs for replacing dead RGCs in glaucoma. Stem Cells 2013;33:1743–1758
- Subjects :
- Retinal Ganglion Cells
genetic structures
Induced Pluripotent Stem Cells
Cell- and Tissue-Based Therapy
Mice, SCID
Biology
Retinal ganglion
Article
chemistry.chemical_compound
medicine
Animals
Progenitor cell
Induced pluripotent stem cell
Retina
Peripheral Nervous System Diseases
Glaucoma
Retinal
Cell Biology
Anatomy
Cellular Reprogramming
eye diseases
Mice, Inbred C57BL
Transplantation
Disease Models, Animal
medicine.anatomical_structure
chemistry
Molecular Medicine
Ocular Hypertension
sense organs
Stem cell
Neuroscience
Reprogramming
Developmental Biology
Subjects
Details
- ISSN :
- 15494918 and 10665099
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Stem Cells
- Accession number :
- edsair.doi.dedup.....47df0ff8c40afb3eee24649467008b9d