title: Vasoactive intestinal peptide induction by ciliary neurotrophic factor in donor human corneal endothelium in situ.
abstract: After peripheral nerve axotomy, vasoactive intestinal peptide (VIP) gene expression is upregulated in neurons, whereas ciliary neurotrophic factor (CNTF) accumulates extracellularly at the lesion site. Although CNTF-induced VIP gene expression has been reported in cultured sympathetic neurons and neuroblastoma cells, it still remains to be determined if CNTF and VIP play interrelated roles in nerve injury. The corneal endothelium, like sympathetic neurons, derives from the neural crest. Previously, we demonstrated that a sublethal-level of oxidative stress induces CNTF release from corneal endothelial (CE) cells in situ. Here, we show that human CE cells express the 53 kDa ligand-binding alpha subunit of the CNTF receptor (CNTFRalpha). We further demonstrate that CNTF induces VIP immunoreactivity in human donor corneas. To determine if the increase in VIP immunoreactivity was reflected by an increase in gene expression, donor human corneas were bisected and treated with CNTF or vehicle, and analyzed by real-time RT-qPCR. Two experiments using different sets of bisected corneas indicated that CNTF induced increases in VIP mRNA levels of 6.5+/-2.2-fold (N=7 corneas) and 2.3+/-0.6-fold (N=10 corneas) (mean+/-S.E.M.), respectively. Whereas VIP is produced as a CE autocrine factor against oxidative stress, the present study suggested that oxidative stress-released CNTF plays a role in protecting CE cells against oxidative stress injury by upregulating VIP expression.
authors: Department of Ophthalmology & Visual Sciences, University of Maryland, Baltimore, United States. skoh@umaryland.edu
authors: Shay-Whey M
authors: SW
authors: Koh
authors: Yan
authors: Y
authors: Guo
authors: Steve L
authors: SL
authors: Bernstein
authors: James A
authors: JA
authors: Waschek
authors: Xiuhuai
authors: X
authors: Liu
authors: Aviva J
authors: AJ
authors: Symes
mesh_terms: D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis*
chemical_list: D020934:Ciliary Neurotrophic Factor; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide
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