Purchase this article with an account.
A.C. Morris, T. Scholz, J.M. Fadool; Rod Progenitor Proliferation In A Transgenic Zebrafish Model Of Rod Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5756.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
An understanding of the molecular mechanisms that regulate stem cell proliferation and differentiation would be beneficial to research aimed at stimulating neural repair following human CNS injury. It is well known that the eyes of teleost fish continue to grow as the animal ages; as the retina expands within the growing eye, most new retinal neurons are generated from a region of persistent neurogenesis at the retinal margin. Rod photoreceptors, however, differentiate from a pool of rod progenitor cells scattered across the outer nuclear layer (ONL). Moreover, in response to retinal damage, regeneration of retinal tissue occurs following an increase in rod progenitor proliferation. Previous work in goldfish suggests that the insulin–like growth factor–I (IGF–1) signaling pathway may play a role in the regulation of rod progenitor proliferation. The purpose of this work was to characterize the development and regulation of the rod progenitor response in XOPS–mCFP transgenic zebrafish, which experience selective rod degeneration early in development.
Rod degeneration and cone survival in the zebrafish XOPS–mCFP transgenic line has been described previously (Morris et al., 2005). Larval and adult retinal cryosections from wild–type and transgenic animals were immunolabeled with the rod–specific antibody 4C12 and with an antibody to PCNA to detect proliferating cells. Sections were observed by fluorescence microscopy. Expression of IGF signal transduction pathway genes was analyzed by RT–PCR and by in situ hybridization of frozen retinal sections.
In retinas of adult XOPS–mCFP zebrafish, a large increase in rod progenitor proliferation relative to wild–type animals was observed. The presence of PCNA–positive rod progenitors was not detected in wild–type or transgenic zebrafish up to 21 dpf. However, by three months post fertilization (mpf), PCNA–positive progenitor cells were observed in wild–type retinas, as well as an upregulation of progenitor proliferation in transgenic retinas. RT–PCR of RNA isolated from wild–type and XOPS–mCFP adult retinas revealed and increase in both IGF–I and IGF–1 receptor (IGF–1R) expression in transgenic retinas.
Selective loss of rod photoreceptors in XOPS–mCFP transgenic animals causes an upregulation of rod progenitor proliferation. The stimulus that induces the hyperproliferation of rod progenitors in transgenic animals is not mature before 21 dpf, but does become active by 3 mpf. Induction of rod progenitor proliferation in transgenic animals may involve the IGF–1 signaling pathway.
This PDF is available to Subscribers Only