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Enrique J. de la Rosa, Jimena Baleriola, Noemi Alvarez, Jose L. San-Martin, Teresa Suarez, Gloria Terrados, Beatriz Escudero, Antonio Bernad, Luis Blanco; Requirement of DNA Double-strand Break Repair in Retinal Neurogenesis and Axonogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6002.
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© ARVO (1962-2015); The Authors (2016-present)
Programmed cell death is a genuine process of retinal development that affects all cell types including progenitors, young neurons, as well as mature neurons and glial cells. However, the process underlying the death of recently differentiated neurons during neurogenesis is not established. Several genetically-modified mouse model systems defective in DNA double-strand break repair present a dramatic effect on early nervous system development, suggesting a possible involvement of DNA repair in neural development. Hereby, we try to demonstrate in vivo the requirement of DNA repair for proper retinal neurogenesis.
We have analyzed the embryonic retina in two mouse models deficient for DNA repair, namely Pol mu and SCID, as well as in their wild type counterparts. Whole mount and dissociated retinas were processed for immunohistochemistry and TUNEL to determine the effect of the mutations on DNA repair, neuronal differentiation, axonogenesis and cell death.
Both Pol mu and SCID mutants showed distorted DNA repair and an increase in apoptotic cell death that selectively affected young retinal ganglion cells. Further, the pattern of axonal growth into the retina and the optic nerve was also altered.
Our results support the requirement of balanced DNA double-strand break generation and repair during retinal neurogenesis in order to achieve correct retinal development. Further, the occurrence of double-strand breaks seems to underlie the process of early neural cell death.
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