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Latanoprost Promotes Neurite Outgrowth in Differentiated RGC-5 Cells via the PI3K-Akt-mTOR Signaling Pathway

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Abstract

Latanoprost, a synthetic derivative of the natural prostaglandin F2a (PGF2a), is a powerful antiglaucoma agent with ocular hypotensive and neuroprotective effects. However, the neuroregenerative effect and signaling pathway of latanoprost in retinal ganglion cells (RGCs) are still unknown. The purpose of this study is to investigate the regenerative effect of latanoprost in differentiated RGC-5 cells and its underlying mechanisms. Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay and neurite length was examined by ArrayScan HCS Reader and Neurite outgrowth BioApplication. Expressions of Akt phosphorylation (p-Akt) and mammalian target of rapamycin phosphorylation (p-mTOR) were investigated by Western blot analysis. The results indicated that 0.1 μM latanoprost (at a clinically therapeutic concentration) significantly increased cell viability as compared with control. Meanwhile, 0.1 μM latanoprost resulted in the obvious promotion of neurite outgrowth similar to ciliary neurotrophic factor (CNTF) and simultaneously increased the levels of p-Akt and p-mTOR expression. The effects of latanoprost were blocked by the Prostaglandin F receptor (FP receptor) inhibitor AL8810, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and the mTOR inhibitor rapamycin. This study presents novel in vitro evidence that latanoprost could promote neurite outgrowth through an FP receptor-mediated modulation of the PI3K-Akt-mTOR signaling pathway. This finding may provide insight into a better understanding of a new mechanism of latanoprost for glaucoma therapy and into the physiological-modulating activities of prostaglandins.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 30700280), the National Basic Research Program of China (No. 2010CB529806), the Shanghai Municipal Science and Technology Commission (No. 09ZR1416000), and the Shanghai Leading Academic Discipline Project (No. S30205).

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China

    Jun Zheng, Xuemei Feng, Lina Hou, Yongyao Cui, Liang Zhu, Jian Ma, Zheng Xia, Wei Zhou & Hongzhuan Chen

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  1. Jun Zheng
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  2. Xuemei Feng
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  3. Lina Hou
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  4. Yongyao Cui
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  7. Zheng Xia
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  8. Wei Zhou
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  9. Hongzhuan Chen
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Correspondence to Wei Zhou or Hongzhuan Chen.

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Zheng, J., Feng, X., Hou, L. et al. Latanoprost Promotes Neurite Outgrowth in Differentiated RGC-5 Cells via the PI3K-Akt-mTOR Signaling Pathway. Cell Mol Neurobiol 31, 597–604 (2011). https://doi.org/10.1007/s10571-011-9653-x

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  • DOI: https://doi.org/10.1007/s10571-011-9653-x

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