PACAP Induces Neurite Outgrowth in Cultured Trigeminal Ganglion Cells and Recovery of Corneal Sensitivity After Flap Surgery in Rabbits

Fukiage, Chiho; Nakajima, Takeshi; Takayama, Yoshiko; Minagawa, Yoko; Shearer, Thomas R.; Azuma, Mitsuyoshi

doi:10.1016/j.ajo.2006.10.034

Cited by 42 publications

(32 citation statements)

References 29 publications

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“…Note that PACAP also stimulated secretion of a tear protein, lactoferrin, in cultured monkey acinar cells [39]. These studies are relevant to treatment of dry eye and recovery from LASIK.…”

Section: Pituitary Adenylate Cyclase-activating Peptide (Pacap)mentioning

confidence: 96%

“…PACAP-27 might be beneficial because of its ability to stimulate TgN neurite outgrowth as well as increase tear protein secretion from the lacrimal gland. Indeed, administration of eye drops containing 10 μM PACAP-27 to an in vivo rabbit model of corneal flap surgery caused extension of neuronal processes from amputated nerve trunks and greatly accelerated recovery of corneal sensitivity [39].…”

Section: Pituitary Adenylate Cyclase-activating Peptide (Pacap)mentioning

confidence: 99%

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Drug Treatment of Corneal Neuropathies: Mini Review

Tr¹,

Azuma²

2017

J Clin Exp Ophthalmol

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“…Note that PACAP also stimulated secretion of a tear protein, lactoferrin, in cultured monkey acinar cells [39]. These studies are relevant to treatment of dry eye and recovery from LASIK.…”

Section: Pituitary Adenylate Cyclase-activating Peptide (Pacap)mentioning

confidence: 96%

Section: Pituitary Adenylate Cyclase-activating Peptide (Pacap)mentioning

confidence: 99%

Drug Treatment of Corneal Neuropathies: Mini Review

Tr¹,

Azuma²

2017

J Clin Exp Ophthalmol

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“…9 Pituitary adenylate cyclase-activating polypeptide (PACAP) also induced outgrowth of neuronal processes in trigeminal ganglion (TG) cells, and PACAP accelerated recovery of corneal sensitivity after creation of a corneal flap in rabbits. 10 Thus, drugs that stimulate bioactive neuropeptides-such as glial cell line-derived neurotrophic factor (GDNF)-involved in corneal regeneration would be potentially useful in therapy for dry eye caused by LASIK surgery.…”

Section: Methodsmentioning

confidence: 99%

“…TG cells were prepared according to a previously reported method with modifications. 10 Briefly, the trigeminal ganglia were minced with scissors and digested for 30 minutes with 3 mg/mL collagenase A (Roche Diagnostics, Basel, Switzerland), and then incubated for 40 minutes in neuronal dispersion liquid (Sumitomo Bakelite, Tokyo, Japan) at 378C. Following filtration through a 40-lm cell strainer (Becton Dickinson, Franklin Lakes, NJ), 10% BSA solution was added, and the cells were pelleted by centrifugation (30 minutes, 1000g).…”

Section: Isolation and Culture Of Tg Cells From Trigeminal Ganglionmentioning

confidence: 99%

FK962 Promotes Neurite Elongation and Regeneration of Cultured Rat Trigeminal Ganglion Cells: Possible Involvement of GDNF

Kishimoto

Yabuta

Shearer

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Amputation of the trigeminal nerve leads to decreased corneal sensitivity and dry eye. Our previous study showed that the drug FK962 (N-[1-acetylpiperidin-4-yl]-4-fluorobenzamide) induced neurite elongation from trigeminal ganglion (TG) cells and accelerated recovery of corneal sensitivity in a rabbit model of in situ keratomileusis (LASIK) surgery. However, the molecular pathways leading to FK962-induced neurite elongation and regeneration are not well defined. Thus, the purposes of the present experiments were to determine if FK962 induces elongation and regeneration of cultured rat TG cells and to investigate the mechanism of FK962-induced neurite elongation.METHODS. Mixed TG cells were cultured with or without FK962, and immunocytochemistry was used to detect stimulation of neurite elongation. Neurite regeneration was also tested in an in vitro model of neuronal ablation. ELISA was used to detect glial cell line-derived neurotrophic factor (GDNF) and somatostatin (SST) release, and mRNA expression was measured by qPCR. Antibody neutralization was used to determine the mechanism for FK962-induced neurite elongation/regeneration.RESULTS. FK962 enhanced elongation and regeneration of neurites in TG neurons. GDNF treatment-induced neurite elongation and GDNF antibody significantly inhibited neurite elongation induced by GDNF and FK962. Nerve growth factor (NGF) treatment also induced neurite elongation, which was inhibited by NGF antibody, but NGF antibody did not inhibit FK962-induced neurite elongation.CONCLUSIONS. Our data suggested that FK962 stimulated induction of GDNF from TG cells. GDNF may be a part of the signaling pathway for FK962-induced neurite elongation/ regeneration in rat TG neurons. (Invest Ophthalmol Vis Sci.

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“…4,5 A growing body of evidence suggests that PACAP can efficiently promote traumatic brain or nerve injury repair and nerve synapse growth and modulate the function of the immune system. 6,7 Pituitary adenylate cyclase-activating polypeptide was strongly upregulated in injured neurons, including motor, sympathetic, and sensory neurons. 8,9 Pituitary adenylate cyclase-activating polypeptide-deficient (knockout, KO) mice exhibited delayed axonal regeneration in a facial nerve crush model, and PACAP administration in vivo can attenuate axon degeneration in central nervous system (CNS) injury models.…”

mentioning

confidence: 99%

A New Recombinant PACAP-Derived Peptide Efficiently Promotes Corneal Wound Repairing and Lacrimal Secretion

Zhao

Wang

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.A new recombinant pituitary adenylate cyclase-activating polypeptide (PACAP)-derived peptide, MPAPO, which has higher stability and PAC1-specific potency, was generated. The actions of MPAPO on corneal wound repairing and lacrimal secretion were examined.METHODS. MPAPO was prepared and identified by gene recombination, high-performance liquid chromatography (HPLC), and electrospray ionization mass spectrometry (ESI-MS). Stability assay was performed by HPLC-ESI-MS. PAC1-specific binding and potency assays were performed using PAC1-CHO cells. C57BL/6 mice and Japanese white rabbits were respectively used to analyze the effects of MPAPO on corneal wound repairing and lacrimal fluid secretion. Tetrazolium-based colorimetric assay (MTT), immunofluorescence, gene microarrays, and Western blot assay were performed to measure the effects of MPAPO on corneal epithelial cell proliferation, synapse growth, and gene differential expression of trigeminal ganglion cells. RESULTS.As compared with the wild PACAP, the in vitro stability and PAC1-specific potency of MPAPO with four mutations (M17L, L27K and M, K, respectively, added to the N-and Cterminus) were increased approximately 31-and 2-fold, respectively. MPAPO can significantly promote the proliferation of mouse corneal epithelium cells and the synapse growth of trigeminal ganglion cells. In experimental animals, MPAPO performed a complete corneal epithelial wound closure in 30 hours and significantly inhibited corneal neovascularization, and the effects were obviously stronger than for wild PACAP and recombinant bovine (rb)-bFGF (an anti-corneal wound drug). Furthermore, MPAPO can increase the lacrimal secretion, which may efficiently improve dry eye.CONCLUSIONS. MPAPO may represent a promising external therapeutic peptide for corneal wound repairing or dry eye.Keywords: gene recombination, pituitary adenylate cyclase activating polypeptide (PACAP)-derived peptide, PAC1 receptor, high stability, corneal wound repairing P ituitary adenylate cyclase-activating polypeptide (PACAP) is one of the important neuropolypeptides and a new member in the secretin/glucagon/vasoactive intestinal peptide (VIP) family.1 Pituitary adenylate cyclase-activating polypeptide is present in two forms, PACAP38 and PACAP27 in vivo, and has 60% homology with VIP, but the capacity of PACAP for stimulating brain pituicytes to generate adenylate cyclase is 1000-fold that of VIP.2 The biological actions of PACAP are mediated through three G protein-coupled receptors, namely, PAC1, VPAC1, and VPAC2. PAC1 is the specific 7-transmembrane receptor and exhibits high affinity for PACAP, but much lower affinity for VIP. VPAC1 and VPAC2 receptors display similar affinity for PACAP and VIP. 3 In mammals, PAC1 and VPAC receptors are expressed in the nervous, gastrointestinal, reproductive, and immune systems. However, PAC1 is mainly expressed in endocrine glands, such as the pituitary and adrenal, in the eye, and in the peripheral nervous system (PNS). In the PNS, especially in many ganglia and axons...

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PACAP Induces Neurite Outgrowth in Cultured Trigeminal Ganglion Cells and Recovery of Corneal Sensitivity After Flap Surgery in Rabbits

Cited by 42 publications

References 29 publications

Drug Treatment of Corneal Neuropathies: Mini Review

Drug Treatment of Corneal Neuropathies: Mini Review

FK962 Promotes Neurite Elongation and Regeneration of Cultured Rat Trigeminal Ganglion Cells: Possible Involvement of GDNF

A New Recombinant PACAP-Derived Peptide Efficiently Promotes Corneal Wound Repairing and Lacrimal Secretion

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