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Proliferation and Expression of Progenitor and Mature Retinal Phenotypes in the Adult Mammalian Ciliary Body after Retinal Ganglion Cell Injury

¹From the Departments of Anatomy and Neurobiology and ³Surgery (Neurosurgery), Dalhousie University, Halifax, Nova Scotia, Canada; and the ²Departments of Neurosurgery and Neurology, MGH-HMS Center for Nervous System Repair, Harvard Medical School, and Program in Neuroscience, Harvard Stem Cell Institute, Harvard University, Boston, Massachusetts.

PURPOSE. Despite the identification of a small population of cells residing in the ciliary body (CB) of the adult mammalian eye that have the capacity to generate retina-like cells in vitro, their activity in vivo remains quiescent. The authors sought to identify whether the predictable and time-dependent death of retinal ganglion cells (RGCs) results in activation of progenitor-like cells within the CB.

METHODS. RGC injury was induced by optic nerve axotomy in adult mice. Thymidine-analogue lineage tracing and immunocytochemistry were used to identify dividing cells and the phenotype of newly generated progeny.

RESULTS. Two populations of nestin-expressing cells are present in the CB of the uninjured eye. One population resides in periendothelial cells of blood vessels, and a second resides in the ciliary epithelium. Axotomy increases proliferation in the CB, a response that begins before the onset of RGC death and continues during a time that corresponds with the peak in RGC death. In addition, a subpopulation of nestin-positive cells in the CB upregulates the homeodomain protein Chx10. Finally, recoverin, the expression of which is normally restricted to photoreceptors and bipolar cells of the retina, is upregulated in the CB in a manner that is independent of proliferation.

CONCLUSIONS. Together, these results suggest that progenitorlike cells of the CB respond to cues associated with the loss of a single retinal cell type and that a subpopulation of those cells may differentiate into a cell that bears phenotypic resemblance to those seen in the retina.

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