All-trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells
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Updated: Mar 1, 2026
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Wen-Di Zhou1,2, Lu-Lu Wang1, Lan-Bo Zhou3
1Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Insights
All-trans retinoic acid (ATRA) boosts ciliary neurotrophic factor (CNTF) in retinal cells, offering a potential treatment for retinopathy of prematurity, a leading cause of infant vision loss.
Area of Science:
- Ophthalmology
- Molecular Biology
- Developmental Biology
Background:
- Retinopathy of prematurity (ROP) is a significant cause of visual impairment in premature infants.
- Ciliary neurotrophic factor (CNTF) supports photoreceptor survival and retinal regeneration.
- CNTF expression is influenced by factors including all-trans retinoic acid (ATRA).
Purpose of the Study:
- To investigate the effect of ATRA on CNTF expression in retinal pigment epithelial (RPE) cells.
- To elucidate the signaling pathways involved in ATRA-mediated CNTF regulation.
- To assess CNTF levels in models of retinopathy of prematurity.
Main Methods:
- Primary mouse RPE cells were treated with ATRA.
- Quantitative analysis of CNTF expression and secretion.
- Investigation of the PKA signaling pathway and CREB binding to the CNTF promoter.
- Analysis of CNTF levels in human serum and mouse models of oxygen-induced retinopathy.
Main Results:
- ATRA increased CNTF expression in RPE cells in a dose- and time-dependent manner.
- The PKA signaling pathway and CREB activation were essential for ATRA-induced CNTF upregulation.
- CNTF levels were reduced in children with ROP and in mice with oxygen-induced retinopathy.
- High oxygen conditions decreased CNTF expression and secretion in RPE cells, which was restored by ATRA treatment.
Conclusions:
- ATRA effectively upregulates CNTF expression and secretion in RPE cells.
- ATRA may serve as a therapeutic agent to restore CNTF levels in retinopathy of prematurity.
- The findings highlight the role of ATRA-CNTF signaling in retinal protection.
Abstract:
Retinopathy of prematurity, a leading cause of visual impairment in low birth-weight infants, remains a crucial therapeutic challenge. Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that promotes rod and cone photoreceptor survival and cone outer segment regeneration in the degenerating retina. Ciliary neurotrophic factor expression is regulated by many factors such as all-trans retinoic acid (ATRA). In this study, we found that ATRA increased CNTF expression in mouse retinal pigment epithelial (RPE) cells in a dose- and time-dependent manner, and PKA signaling pathway is necessary for ATRA-induced CNTF upregulation. Furthermore, we showed that ATRA promoted CNTF expression through CREB binding to its promoter region. In addition, CNTF levels were decreased in serum of retinopathy of prematurity children and in retinal tissue of oxygen-induced retinopathy mice. In mouse RPE cells cultured with high oxygen, CNTF expression and secretion were decreased, but could be recovered after treatment with ATRA. In conclusion, our data suggest that ATRA administration upregulates CNTF expression in RPE cells.
