title: Latanoprost promotes neurite outgrowth in differentiated RGC-5 cells via the PI3K-Akt-mTOR signaling pathway.
abstract: Latanoprost, a synthetic derivative of the natural prostaglandin F(2a) (PGF(2a)), 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.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zheng
authors.forename: Xuemei
authors.initials: X
authors.lastname: Feng
authors.forename: Lina
authors.initials: L
authors.lastname: Hou
authors.forename: Yongyao
authors.initials: Y
authors.lastname: Cui
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xia
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D000077338:Latanoprost; D009025:Morpholines / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002867:Chromones; D000077338:Latanoprost; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D011461:Prostaglandins F, Synthetic; D051057:Proto-Oncogene Proteins c-akt; D011982:Receptors, Prostaglandin; D058570:TOR Serine-Threonine Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one