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S. Bhattacharya, A.V. Das, I. Ahmad; Biphasic Effects of CNTF on Ath3 Expression and Differentiation of Late Retinal Progenitors . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5349.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have shown previously that the differentiation of late retinal progenitors into bipolar cells, is regulated by a neural bHLH transcription factor, Ath3. Evidence suggests that bipolar cell differentiation is also influenced by CNTF. In order to determine the interactions between cell intrinsic and cell extrinsic factors during retinal neurogenesis, we are investigating the effects of CNTF on Ath3 mediated differentiation of late retinal progenitors in–vitro. Methods: Late retinal progenitors, enriched as neurospheres, were cultured in increasing concentrations of CNTF (0–100 ng/mL) for 4–5 days and expression of Ath3 and markers of specific retinal cell types were analyzed by immunocytochemistry and RT–PCR. Similar experiments were carried out in the presence of Ath3 antisence/missence oligonucleotides to ascertain whether or not the effects of CNTF on differentiation are mediated via Ath3. Results: A concentration dependent effect of CNTF on Ath3 expression was observed. Levels of Ath3 transcripts increased in the presence of CNTF up to a concentration of 50ng/mL. The increase in Ath3 expression was followed by an increase in levels of transcripts corresponding to bipolar cell–specific markers. However, at a CNTF concentration higher than 50ng/mL, expression of Ath3 and bipolar cell–specific markers decreased, demonstrating a biphasic effect of CNTF on Ath3 expression and bipolar cell differentiation. We are currently investigating if the increase in concentration of CNTF modulates a shift in neural to glial differentiation during late histogenesis. Conclusions: Signaling mediated by CNTF may act as a molecular switch that regulates differentiation of late retinal progenitors into neurons and glia.
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