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T. Haynes, C. Gutierrez, J.–C. Aycinena, B. Lehman, S. Reddy, A. Abtahi, K. Del Rio–Tsonis; BMP Regulates Multiple Processes During Retina Regeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3817.
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© ARVO (1962-2015); The Authors (2016-present)
The embryonic chick is able to regenerate a complete neural retina after retinectomy between developmental stages 22–24 in the presence of fibroblast growth factor (FGF). The regeneration is complete seven days post–retinectomy and occurs via two distinct mechanisms; transdifferentiation of the RPE and by activation of retinal progenitor cells (RPCs) present in the anterior margin of the eye. Here, we focus on the role of the bone morphogenetic protein (BMP) pathway during retina regeneration from the RPCs.
A retroviral system was used to inhibit and activate the BMP pathway during retina regeneration. Regeneration was assayed 3 and 7 days post–retinectomy. Differentiation of cell types was determined by immunohistochemistry and the level of cell death was determined by TUNEL analysis. Eyes receiving FGF only served as a control for each experiment.
Overexpression of the BMP receptor, BMPR–IA, in the presence of FGF results in an increase in regeneration from the anterior margin and an expansion of the RPCs while inhibiting the BMP pathway by overexpressing noggin in the presence of FGF results in a decrease in regeneration from the anterior margin and a significant reduction in the number of RPCs. Differentiation of all cell types occurs when BMPR–IA is overexpressed with FGF, however, there is an increase in the number of ganglion and amacrine cells and Muller Glia cells are disorganized. Overexpressing noggin affects differentiation even when FGF is present with only photoreceptors and Muller Glia cells present in significant numbers. Apoptosis is significantly increased when BMPR–IA is overexpressed in the presence of FGF especially at later stages of regeneration while no cell death is detected when noggin is overexpressed along with FGF
These results suggest BMP plays multiple roles in the retina regeneration process by regulating proliferation, differentiation and apoptosis of RPCs and their derivatives.
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