Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 1/2017

01-01-2017 | Basic Science

FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells

Authors: Emi Nakajima, Ryan D. Walkup, Thomas R. Shearer, Mitsuyoshi Azuma

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 1/2017

Login to get access

Abstract

Purpose

Corneal sensation, cell proliferation, and wound healing all depend on adequate corneal innervation. Disruption of corneal innervation can lead to dry eye and delayed wound healing. Our studies in rats and rabbits show that the substituted fluorobenzamide drug FK962 accelerates the extension of neuronal processes and recovery of corneal sensitivity. The purpose of the present study was 1) to determine whether FK962 induces sprouting and elongation of neurites in cultured monkey trigeminal ganglion cells, and 2) to investigate the involvement of the neurotrophic peptide GDNF in FK962-induced neurite elongation.

Methods

Dissociated, cultured trigeminal ganglion cells, containing neuronal and Schwann cells were cultured for 48 h with or without FK962. Neuronal elongation was evaluated by immunostaining with a neurofilament-specific antibody. Culture with or without GDNF, or with antibody against GDNF, was used to determine the role of GDNF in FK962-induced neurite elongation.

Results

FK962 or GDNF were found to significantly induce neurite elongation. The GDNF antibody significantly inhibited elongation induced by FK962.

Conclusion

GDNF was found to be a mediator of FK962-induced neurite elongation in a relevant primate model. FK962 may be a candidate drug for treatment of neurotrophic disorders in the human cornea.
Literature
1.
go back to reference Müller LJ, Vrensen GF, Pels L, Cardozo BN, Willekens B (1997) Architecture of human corneal nerves. Invest Ophthalmol Vis Sci 38:985–994PubMed Müller LJ, Vrensen GF, Pels L, Cardozo BN, Willekens B (1997) Architecture of human corneal nerves. Invest Ophthalmol Vis Sci 38:985–994PubMed
3.
go back to reference Goins KM (2005) New insights into the diagnosis and treatment of neurotrophic keratopathy. Ocul Surf 3:96–110CrossRefPubMed Goins KM (2005) New insights into the diagnosis and treatment of neurotrophic keratopathy. Ocul Surf 3:96–110CrossRefPubMed
4.
go back to reference Sigelman S, Friedewald JS (1954) Mitotic and wound-healing activities of the corneal epithelium; effect of sensory denervation. AMA Arch Ophthalmol 52:46–57CrossRefPubMed Sigelman S, Friedewald JS (1954) Mitotic and wound-healing activities of the corneal epithelium; effect of sensory denervation. AMA Arch Ophthalmol 52:46–57CrossRefPubMed
5.
go back to reference Cruzat A, Pavan-Langston D, Hamrah P (2010) In vivo confocal microscopy of corneal nerves: analysis and clinical correlation. Semin Ophthalmol 25:171–177CrossRefPubMedPubMedCentral Cruzat A, Pavan-Langston D, Hamrah P (2010) In vivo confocal microscopy of corneal nerves: analysis and clinical correlation. Semin Ophthalmol 25:171–177CrossRefPubMedPubMedCentral
6.
go back to reference Lee BH, McLaren JW, Erie JC, Hodge DO, Bourne WM (2002) Reinnervation in the cornea after LASIK. Invest Ophthalmol Vis Sci 43:3660–3664PubMed Lee BH, McLaren JW, Erie JC, Hodge DO, Bourne WM (2002) Reinnervation in the cornea after LASIK. Invest Ophthalmol Vis Sci 43:3660–3664PubMed
7.
go back to reference Ueno H, Ferrari G, Hattori T, Saban DR, Katikireddy KR, Chauhan SK, Dana R (2012) Dependence of corneal stem/progenitor cells on ocular surface innervation. Invest Ophthalmol Vis Sci 53:867–872CrossRefPubMedPubMedCentral Ueno H, Ferrari G, Hattori T, Saban DR, Katikireddy KR, Chauhan SK, Dana R (2012) Dependence of corneal stem/progenitor cells on ocular surface innervation. Invest Ophthalmol Vis Sci 53:867–872CrossRefPubMedPubMedCentral
8.
go back to reference Toda I (2007) LASIK and dry eye. Compr Ophthalmol Updat 8:79–85, discussion 87-89 Toda I (2007) LASIK and dry eye. Compr Ophthalmol Updat 8:79–85, discussion 87-89
9.
go back to reference Fukiage C, Nakajima T, Takayama Y, Minagawa Y, Shearer T, Azuma M (2007) PACAP induces neurite outgrowth in cultured trigeminal ganglion cells and recovery of corneal sensitivity after flap surgery in rabbits. Am J Ophthalmol 143:255–262CrossRefPubMed Fukiage C, Nakajima T, Takayama Y, Minagawa Y, Shearer T, Azuma M (2007) PACAP induces neurite outgrowth in cultured trigeminal ganglion cells and recovery of corneal sensitivity after flap surgery in rabbits. Am J Ophthalmol 143:255–262CrossRefPubMed
10.
go back to reference Nakajima E, Walkup RD, Fujii A, Shearer TR, Azuma M (2013) Pituitary adenylate cyclase-activating peptide induces neurite outgrowth in cultured monkey trigeminal ganglion cells: involvement of receptor PAC1. Mol Vis 19:174–183PubMedPubMedCentral Nakajima E, Walkup RD, Fujii A, Shearer TR, Azuma M (2013) Pituitary adenylate cyclase-activating peptide induces neurite outgrowth in cultured monkey trigeminal ganglion cells: involvement of receptor PAC1. Mol Vis 19:174–183PubMedPubMedCentral
11.
go back to reference Tokita K, Inoue T, Yamazaki S, Wang F, Yamaji T, Matsuoka N, Mutoh S (2005) FK962, a novel enhancer of somatostatin release, exerts cognitive-enhancing actions in rats. Eur J Pharmacol 527:111–120CrossRefPubMed Tokita K, Inoue T, Yamazaki S, Wang F, Yamaji T, Matsuoka N, Mutoh S (2005) FK962, a novel enhancer of somatostatin release, exerts cognitive-enhancing actions in rats. Eur J Pharmacol 527:111–120CrossRefPubMed
12.
go back to reference Kishimoto Y, Yabuta C, Shearer TR, Azuma M (2012) FK962 promotes neurite elongation and regeneration of cultured rat trigeminal ganglion cells: possible involvement of GDNF. Invest Ophthalmol Vis Sci 53:5312–5319CrossRefPubMed Kishimoto Y, Yabuta C, Shearer TR, Azuma M (2012) FK962 promotes neurite elongation and regeneration of cultured rat trigeminal ganglion cells: possible involvement of GDNF. Invest Ophthalmol Vis Sci 53:5312–5319CrossRefPubMed
13.
go back to reference Geenen K, Favoreel HW, Nauwynck HJ (2005) Higher resistance of porcine trigeminal ganglion neurons towards pseudorabies virus-induced cell death compared with other porcine cell types in vitro. J Gen Virol 86:1251–1260CrossRefPubMed Geenen K, Favoreel HW, Nauwynck HJ (2005) Higher resistance of porcine trigeminal ganglion neurons towards pseudorabies virus-induced cell death compared with other porcine cell types in vitro. J Gen Virol 86:1251–1260CrossRefPubMed
14.
go back to reference Yabuta C, Oka T, Kishimoto Y, Ohtori A, Yoshimatsu A, Azuma M (2012) Topical FK962 facilitates axonal regeneration and recovery of corneal sensitivity after flap surgery in rabbits. Am J Ophthalmol 153:651–660CrossRefPubMed Yabuta C, Oka T, Kishimoto Y, Ohtori A, Yoshimatsu A, Azuma M (2012) Topical FK962 facilitates axonal regeneration and recovery of corneal sensitivity after flap surgery in rabbits. Am J Ophthalmol 153:651–660CrossRefPubMed
15.
go back to reference Taniwaki T, Schwartz JP (1995) Somatostatin enhances neurofilament expression and neurite outgrowth in cultured rat cerebellar granule cells. Brain Res Dev Brain Res 88:109–116CrossRefPubMed Taniwaki T, Schwartz JP (1995) Somatostatin enhances neurofilament expression and neurite outgrowth in cultured rat cerebellar granule cells. Brain Res Dev Brain Res 88:109–116CrossRefPubMed
16.
go back to reference Airaksinen MS, Saarma M (2002) The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 3:383–394CrossRefPubMed Airaksinen MS, Saarma M (2002) The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 3:383–394CrossRefPubMed
17.
go back to reference Brock JH, Rosenzweig ES, Blesch A, Moseanko R, Havton LA, Edgerton VR, Tuszynski MH (2010) Local and remote growth factor effects after primate spinal cord injury. J Neurosci 30:9728–9737CrossRefPubMedPubMedCentral Brock JH, Rosenzweig ES, Blesch A, Moseanko R, Havton LA, Edgerton VR, Tuszynski MH (2010) Local and remote growth factor effects after primate spinal cord injury. J Neurosci 30:9728–9737CrossRefPubMedPubMedCentral
18.
go back to reference Matsuoka N, Aigner TG (1997) Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks. J Pharmacol Exp Ther 263:436–444 Matsuoka N, Aigner TG (1997) Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks. J Pharmacol Exp Ther 263:436–444
19.
go back to reference Calabrese EJ (2008) Dose-response features of neuroprotective agents: an integrative summary. Crit Rev Toxicol 38:253–348CrossRefPubMed Calabrese EJ (2008) Dose-response features of neuroprotective agents: an integrative summary. Crit Rev Toxicol 38:253–348CrossRefPubMed
20.
go back to reference Nicole O, Ali C, Docagne F, Plawinski L, MacKenzie E, Vivien D, Buisson A (2001) Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J Neurosci 21:3024–3033PubMed Nicole O, Ali C, Docagne F, Plawinski L, MacKenzie E, Vivien D, Buisson A (2001) Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J Neurosci 21:3024–3033PubMed
21.
go back to reference Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK (2013) GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 138:155–175CrossRefPubMed Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK (2013) GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 138:155–175CrossRefPubMed
23.
go back to reference Nielsen J, Gotfryd K, Li S, Kulahin N, Soroka V, Rasmussen KK, Bock E, Berezin V (2009) Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF. J Neurosci 29:11360–11376CrossRefPubMed Nielsen J, Gotfryd K, Li S, Kulahin N, Soroka V, Rasmussen KK, Bock E, Berezin V (2009) Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF. J Neurosci 29:11360–11376CrossRefPubMed
24.
go back to reference Omoto M, Yoshida S, Miyashita H, Kawakita T, Yoshida K, Kishino A, Kimura T, Shibata S, Tsubota K, Okano H, Shimmura S (2012) The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration and sensitivity in a murine corneal transplantation model. PLoS ONE 7:e47716CrossRefPubMedPubMedCentral Omoto M, Yoshida S, Miyashita H, Kawakita T, Yoshida K, Kishino A, Kimura T, Shibata S, Tsubota K, Okano H, Shimmura S (2012) The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration and sensitivity in a murine corneal transplantation model. PLoS ONE 7:e47716CrossRefPubMedPubMedCentral
25.
go back to reference Wanigasekara Y, Keast JR (2006) Nerve growth factor, glial cell line-derived neurotrophic factor and neurturin prevent semaphorin 3A-mediated growth cone collapse in adult sensory neurons. Neuroscience 142:369–379CrossRefPubMed Wanigasekara Y, Keast JR (2006) Nerve growth factor, glial cell line-derived neurotrophic factor and neurturin prevent semaphorin 3A-mediated growth cone collapse in adult sensory neurons. Neuroscience 142:369–379CrossRefPubMed
Metadata
Title
FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells
Authors
Emi Nakajima
Ryan D. Walkup
Thomas R. Shearer
Mitsuyoshi Azuma
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 1/2017
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-016-3525-5

Other articles of this Issue 1/2017

Graefe's Archive for Clinical and Experimental Ophthalmology 1/2017 Go to the issue