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| Research Interests |
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The ability to regenerate differentiated tissues when lost due to disease or other factors is desirable yet rare among adult vertebrates. For example, regeneration of the lens of the eye is restricted to a small number of urodeles (tailed aquatic amphibia). One of these, the Eastern (U.S.) spotted newt, Notophthalmus viridescens, is easily obtainable and has been the subject of research in regeneration of adult eye tissues for most of this century. When the lens is removed, a new lens will form at the margin of the dorsal iris only, in situ; the ventral iris will not regenerate a lens. This new lens resembles the original not only histologically, but also biochemically, in that the lens structural proteins, crystallins, are also present. The source of the this lens is the fully differentiated and non-dividing pigmented epithelium of the dorsal iris which, upon lentectomy, depigments and re-enters the cell cycle.
The finding that the dorsal iris epithelial cells (DI), after lentectomy, undergo seven cell cycles in the time that the ventral iris epithelial cells (VI) undergo three to four cell cycles suggested that this capacity for lens regeneration may be related to mitogenic activity. The fibroblast growth factors (FGFs), present in mammalian and bird ocular tissues, are candidates for such a role. FGFs and their receptors are present and involved in lens regeneration and the receptors may be the limiting elements in this process. There is no apparent hindrance to the equal availability of FGFs (from retina, iris or other eye tissues) to both dorsal and ventral iris. We have demonstrated that FGF receptors are present and operative in lens regeneration, since receptor-directed mitotoxins inhibit regeneration; heterogeneity and differential density in FGF-binding and receptor localization in irs sectors (greater in dorsal) is also present. We propose that the spatial distribution of FGF receptors, especially the amphibian homolog of FGFR-3, is important in initiation of regeneration of eye lens.
We are now also investigating events occurring upstream of FGF and FGF-R activation. It is known that transcription factors, especially those expressed by homeobox genes, are involved in eye development and establishment of head and dorsal-ventral polarity in vertebrates. We have examined expression of two of these factors, PAX-6 and OTX-2, in development and regeneration of eye tissues. Using an adaptation of the proprietary NEN Tyramide Fluorescence Amplification System, we have been able to localize expression of PAX-6 and OTX-2 in embryonic and regenerating adult N. Viridescens lens and retina, the latter also able to regenerate after removal. Heterologous monoclonal antibodies to these factors can bind and be detected with immunofluorescence. OTX-2 and PAX-6 can be found in exactly complementary areas of the presumptive inner and outer embryonic retina; and in the trilaminar, histologically undifferentiated retinal regenerate 16 days after retina removal in the adult. Thus, expression of PAX-6 and OTX-2 signals acquisition of retinal specificity. Results seen in lens development and regeneration are still being analyzed. Lastly, our laboratory is also interested in the development and evolution of vertebrate photoreceptors (rods and cones), and their visual pigments, especially rod opsin. Their embryonic appearance and localization in lower vertebrates have been accomplished. These rsults are useful, especially as markers, in our ongoing studies of eye developmental and regenerative mechanisms. |
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| Selected Publications
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McDevitt, D.S., Brahma, S.K., Jeanny, J.C., and Hicks, D. 1993. Presence and foveal enrichment of rod opsin in the "all-cone" retina of the American chameleon. Anat. Rec. (Molec. Cell. Biol.) 237:299-307. McDevitt, D.S., Brahma, S.K., and Jeanny, J.C. 1993. Embryonic appearance of rod opsin in the urodelan amphibian eye. Roux's Arch. Dev. Biol. 203:164-168. McDevitt, D.S., Brahma, S.K., and Courtois, Y., and Jeanny, J.C. 1997. Fibroblast growth factor receptors and regeneration of the eye lens. Devel. Dyn. 208:220-226. McDevitt, D.S., Brahma, S.K., and Courtois, Y., and Jeanny, J.C. 1998. Eye lens regeneration and FGF-Receptors. Int. J. Dev. Biol., In press. Borst, D.E. and McDevitt, D.S. 2000. Crystallins of sequenctially regenerated adult new eye lenses. Submitted for publication (Development, Genes and Evolution). |
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