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Chris Zelinka, Zachary A Goodman, William A Bishop, Andrew J Fischer; PTEN/mTor-signaling and the formation of Müller glia-derived retinal progenitors. Invest. Ophthalmol. Vis. Sci. 2014;55(13):831.
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The Akt/mTor pathway is an important cell-signaling pathway that can influence many cellular processes including growth and proliferation. During the development of the eye, Akt/mTor-signaling is known to have important context-specific functions. However, there is a paucity of information regarding the roles that Akt/mTor-signaling plays in the mature retina. Accordingly, we investigate the roles of the Akt/mTor pathway in the formation of Müller glia-derived progenitor cells (MGPCs) in the retina in the chick model system in vivo.
: Immunocytochemistry was used to characterize the expression of pS6 (an effector and readout of the Akt/mTor pathway) in developing, mature and damaged chick retinas. The PTEN-inhibitor (VO-OHpic trihydrate) or mTor-inhibitor (rapamycin) were injected into the vitreous chamber of normal and damaged eyes. Retinas were processed for cell proliferation and glial reactivity. Retinal damage was induced by an intraocular injection of N-Methyl-D-aspartate (NMDA).
pS6 is widely expressed by differentiating cells in embryonic retina, but there are minimal levels in a mature, normal retina. Upon excitotoxic damage, pS6 in Müller glia is highly up-regulated within 4hrs after damage and remains elevated for 2 days. This up-regulation of pS6 was blocked by rapamycin. Treatment with PTEN-inhibitor increased, while treatment with rapamycin inhibited, the number of proliferating MGPCs.
Akt/mTor-signaling in mature Müller glial regulates the ability of these glia to become proliferating progenitor-like cells. We conclude that the Akt pathway is not active in a normal retina, the Akt/mTOR pathway is rapidly activated in Müller glia in damaged retinas, and the activation of this pathway is required for the formation of MGPCs.
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