Abstract
Abstract: :
Purpose: In response to acute damage, Müller glia in the chicken retina have been shown to be a source of proliferating progenitor–like cells (Fischer and Reh, 2001). The secreted factors and signaling pathways that regulate this process remain unknown. The purpose of this study was to test whether secreted factors, that are known to promote glial differentiation during development, regulate the ability of Müller glia to proliferate and become retinal progenitors in response to acute damage in a mature retina. Methods: We made intraocular injections of BMP4, EGF or CNTF before or after a single, toxic dose of NMDA and assayed for proliferating Müller glia–derived cells within the retina. We assayed for proliferation by using BrdU–immunolabeling in frozen sections of the retina. Results: Injections of BMP4 or CNTF, but not EGF, before NMDA–treatment reduced the number of Müller glia that proliferated and transdifferentiated into progenitor–like cells. These factors also greatly reduced the number of apoptotic nuclei in toxin–treated retinas. However, these effects were transient for BMP4, but not for CNTF. Injections of CNTF 5 days prior NMDA–treatment suppressed glial proliferation and transdifferentiation, while injections of BMP4 in this paradigm had no effect. In addition, CNTF injected after NMDA–treatment suppressed glial proliferation, while BMP4 did not. Conclusions: We propose that the ability of Müller glia to re–enter the cell cycle can be controlled by intraocular injections of BMP4 and CNTF. It is possible that these factors normally play a role in regulating the ability of glia to proliferate in response to neural damage.
Keywords: retinal glia • growth factors/growth factor receptors • neuroprotection