Abstract
Abstract: :
Purpose: Pax6 is the mammalian orthologue of eyeless, the master gene for eye morphogenesis and evolution in drosophila. Targeted expression of eyeless in Drosophila leads to the formation of ectopic functional eyes and normal expression of PAX6 in mammals is essential for correct eye development. Little is known about potential roles of PAX6 in the adult, senile or degenerative mammalian retina. We have therefore investigated PAX6 levels and localization in the aged human and mouse retina and tested Pax6 gene expression in a model of retinal degeneration. Methods: Retinas from humans (age range 11 to 76 years) and retinas from B6/129S mice (postnatal day 5 to 428) were used for analysis. Levels of PAX6 protein in mouse and human retinas were determined by Western blot analysis of total retinal protein extracts using a polyclonal antibody raised against quail PAX6 (Carrière et al., 1993). The expression pattern of PAX6 in human retina was determined by immunohistochemistry on retinal cryo-sections using the identical antibody. Expression of Pax6 in a mouse model of retinal degeneration (induced by illumination with white fluoresent light of 15'000 lux for 2 hours) was analyzed by exponential RT-PCR. Results: In human retinas, PAX6 was predominantly localized to the ganglion cell layer and expression was detected up to 64 years of age. In mouse retinas, PAX6 protein levels were high at P5, decreased to intermediate levels at P21 and remained constant thereafter at least to P428. In the light-induced degenerative mouse retina Pax6 mRNA showed a slight but significant decrease to 60% of control levels at 6 hours after illumination. Conclusion: Pax6, the master gene of eye development, remains distinctly expressed in the ageing mammalian retina suggesting a distinct role of PAX6 in the retina after completion of eye morphogenesis. Pax6 might be involved in the maintenance of a correct retinal morphology and/or function. Furthermore, the observed decrease of Pax6 mRNA during light-induced retinal degeneration might indicate that downregulation of PAX6 might be a co-factor promoting degenerative eye diseases. Supported by the Swiss National Science Foundation, German National Science Foundation.
Keywords: 417 gene/expression • 561 retinal degenerations: cell biology • 564 retinal development