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Katia Del Rio-Tsonis, Tracy Haynes, Apostolia Tzekou, Agustin Luz Madrigal, Nancy P. Echeverri, Panagiotis Tsonis, John D. Lambris; The Role of Complement in Retina Regeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2254.
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The embryonic chick can regenerate its retina after complete removal via the reprogramming of the Retinal Pigmented Epithelium (RPE) or by the activation of retinal stem/progenitor cells present in the anterior margin of the eye. We have shown that several different signaling pathways regulate this regenerative process. In the past, we have shown that the Complement components, C3 and C5, are expressed during limb and lens regeneration in salamanders (Del Rio-Tsonis et al., 1998; Kimura et al., 2003). The timing of this expression might indicate that it is correlated with the process of dedifferentiation and production of embryonic/stem cell-like cells. The purpose of this study is to explore the possible role of the critical components C3/C3a and C5/C5a in chick retina regeneration.
In situ hybrization and immunohistochemistry were used as tools to study the expression pattern of these molecules during chick eye development and retina regeneration. We have also used laser capture microdissection and RTPCR to detect the mRNA for the complement components in the different tissues of the developing eye as well as during regeneration. In addition, we have generated chick C3a and C5a peptides and injected them in the eye cavity post-retina removal in the absence of any growth factors to assess their regenerative potential. Eyes undergoing retina regeneration were collected at different stages of regeneration and processed for histology and immunohistochemistry.
Expression of the complement components and the anaphylotoxin receptors was demonstrated in intact embryonic eyes as well as in eyes undergoing different stages of retina regeneration. The expression of C3, C5, C3aR and C5aR has been confirmed by in situ hybridization and via RTPCR. Surprisingly, we found that C3a and C5a are able to induce retina regeneration via activation of stem/progenitor cells or via the reprogramming of RPE cells in the absence of any growth factors. We will discuss possible mechanisms by which Complement components C3a and C5a induce retina repair and regeneration.
Complement components are present in the chick developing eye as well as in eyes undergoing retina regeneration. C3a and C5a are able to induce retina regeneration in the absence of exogenous FGF. These results suggest complement factors may induce retina regeneration by a novel mechanism independent of the FGF pathway.
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