{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:59:41Z","timestamp":1791928781682,"version":"4.3.4"},"reference-count":60,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"1","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2021,1,22]]},"DOI":"10.1167\/iovs.62.1.23","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T16:48:59Z","timestamp":1611420539000},"page":"23","source":"Crossref","is-referenced-by-count":17,"title":["Pigment Epithelium-Derived Factor Peptide Promotes Corneal Nerve Regeneration: An In Vivo and In Vitro Study"],"prefix":"10.1167","volume":"62","author":[{"given":"Shu-I","family":"Yeh","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hsun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Advanced Ocular Surface and Corneal Nerve Research Center, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Sang","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Advanced Ocular Surface and Corneal Nerve Research Center, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Te","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Advanced Ocular Surface and Corneal Nerve Research Center, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Ophthalmology, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeou-Ping","family":"Tsao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City, Taiwan"},{"name":"Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Min","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Advanced Ocular Surface and Corneal Nerve Research Center, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Ophthalmology, College of Medicine, National Taiwan University; Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves: structure, contents, and function","volume":"76","author":"Muller","year":"2003","journal-title":"Exp Eye Res"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1167\/iovs.15-18019","article-title":"Neuroanatomy and neurochemistry of mouse cornea","volume":"57","author":"He","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib3","first-page":"3660","article-title":"Reinnervation in the cornea after LASIK","volume":"43","author":"Lee","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1001\/archopht.125.12.1693","article-title":"Keratocyte density and recovery of subbasal nerves after penetrating keratoplasty and in late endothelial failure","volume":"125","author":"Patel","year":"2007","journal-title":"Arch Ophthalmol"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1097\/00055735-199908000-00009","article-title":"Management of neurotrophic keratopathy","volume":"10","author":"Lambiase","year":"1999","journal-title":"Curr Opin Ophthalmol"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"5144","DOI":"10.1158\/0008-5472.CAN-04-3744","article-title":"Two functional epitopes of pigment epithelial-derived factor block angiogenesis and induce differentiation in prostate cancer","volume":"65","author":"Filleur","year":"2005","journal-title":"Cancer Res"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/(SICI)1097-4547(19990915)57:6<>1.0.CO;2-C","article-title":"Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death","volume":"57","author":"Cao","year":"1999","journal-title":"J Neurosci Res"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1002\/(SICI)1097-4547(19990615)56:6<>1.0.CO;2-M","article-title":"Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons","volume":"56","author":"DeCoster","year":"1999","journal-title":"J Neurosci Res"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/(ISSN)1096-9861","article-title":"Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons","volume":"412","author":"Houenou","year":"1999","journal-title":"J Comp Neurol"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"9378","DOI":"10.1523\/JNEUROSCI.22-21-09378.2002","article-title":"Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons","volume":"22","author":"Bilak","year":"2002","journal-title":"J Neurosci"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"6742","DOI":"10.1167\/iovs.14-14696","article-title":"PEDF improves mitochondrial function in RPE cells during oxidative stress","volume":"55","author":"He","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1076\/ceyr.22.4.245.5506","article-title":"Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury","volume":"22","author":"Ogata","year":"2001","journal-title":"Curr Eye Res"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1073\/pnas.031252398","article-title":"Prevention of ischemia-induced retinopathy by the natural ocular anti-angiogenic agent pigment epithelium-derived factor","volume":"98","author":"Stellmach","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nn1657","article-title":"Pigment epithelium-derived factor is a niche signal for neural stem cell renewal","volume":"9","author":"Ramirez-Castillejo","year":"2006","journal-title":"Nat Neurosci"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/978-1-4419-1399-9","article-title":"PEDF promotes retinal neurosphere formation and expansion in vitro","volume":"664","author":"De Marzo","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1167\/iovs.10-6413","article-title":"Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes retinal progenitor cell survival","volume":"52","author":"Zhu","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3727\/215517914X679265","article-title":"Human menstrual blood-derived mesenchymal cells as new human feeder layer system for human embryonic stem cells","volume":"7","author":"Silva Dos Santos","year":"2014","journal-title":"Cell Med"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1002\/stem.1393","article-title":"PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing","volume":"31","author":"Ho","year":"2013","journal-title":"Stem Cells"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"C159","DOI":"10.1152\/ajpcell.00344.2014","article-title":"PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells","volume":"309","author":"Ho","year":"2015","journal-title":"Am J Physiol Cell Physiol"},{"key":"bib20","first-page":"1114","article-title":"Pigment epithelium-derived factor (PEDF) peptide promotes the expansion of hepatic stem\/progenitor cells via ERK and STAT3-dependent signaling","volume":"9","author":"Shih","year":"2017","journal-title":"Am J Transl Res"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.exer.2012.07.008","article-title":"Lipoxin A(4) inhibits platelet-activating factor inflammatory response and stimulates corneal wound healing of injuries that compromise the stroma","volume":"103","author":"Kakazu","year":"2012","journal-title":"Exp Eye Res"},{"key":"bib22","article-title":"The effect of human platelet lysate on corneal nerve regeneration [published online ahead of print Nov 20, 2019]","author":"Huang","journal-title":"Br J Ophthalmol"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"29574","DOI":"10.18632\/oncotarget.v8i18","article-title":"Rapamycin promotes differentiation increasing betaIII-tubulin, NeuN, and NeuroD while suppressing nestin expression in glioblastoma cells","volume":"8","author":"Ferrucci","year":"2017","journal-title":"Oncotarget"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s004410051013","article-title":"Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in the human fetal brain","volume":"291","author":"Ulfig","year":"1998","journal-title":"Cell Tissue Res"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"15820","DOI":"10.1038\/ncomms15820","article-title":"Different populations of CD11b(+) dendritic cells drive Th2 responses in the small intestine and colon","volume":"8","author":"Mayer","year":"2017","journal-title":"Nat Commun"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1046\/j.1463-5224.2001.00189.x","article-title":"A comparison of corneal sensitivity between brachycephalic and domestic short-haired cats","volume":"4","author":"Blocker","year":"2001","journal-title":"Vet Ophthalmol"},{"key":"bib27","article-title":"The effect of human platelet lysate on corneal nerve regeneration [published online ahead of print Nov 20, 2019]","author":"Huang","journal-title":"Br J Ophthalmol"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/978-1-4939-7237-1","article-title":"Isolation, purification, and culture of primary murine sensory neurons","volume":"1656","author":"Katzenell","year":"2017","journal-title":"Methods Mol Biol"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1744-8069-2-11","article-title":"Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal neurons and their modulation by NGF or serotonin","volume":"2","author":"Simonetti","year":"2006","journal-title":"Mol Pain"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41374-018-0118-4","article-title":"Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4","volume":"99","author":"Okada","year":"2019","journal-title":"Lab Invest"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1136\/bjo.2009.173799","article-title":"Architecture and distribution of human corneal nerves","volume":"94","author":"Al-Aqaba","year":"2010","journal-title":"Br J Ophthalmol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.exer.2009.12.010","article-title":"Anatomy of the human corneal innervation","volume":"90","author":"Marfurt","year":"2010","journal-title":"Exp Eye Res"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.survophthal.2013.09.002","article-title":"Corneal nerves in health and disease","volume":"59","author":"Shaheen","year":"2014","journal-title":"Surv Ophthalmol"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/0014-4886(80)90154-5","article-title":"Sensory denervation of the rabbit cornea affects epithelial properties","volume":"69","author":"Beuerman","year":"1980","journal-title":"Exp Neurol"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1001\/archopht.1954.00920050048005","article-title":"Mitotic and wound-healing activities of the corneal epithelium; effect of sensory denervation","volume":"52","author":"Sigelman","year":"1954","journal-title":"AMA Arch Ophthalmol"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3109\/02713689408995778","article-title":"Epithelial wound healing in the denervated cornea","volume":"13","author":"Araki","year":"1994","journal-title":"Curr Eye Res"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/S0161-6420(90)32587-3","article-title":"Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis","volume":"97","author":"Gilbard","year":"1990","journal-title":"Ophthalmology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.preteyeres.2018.04.003","article-title":"Neurotrophic keratopathy","volume":"66","author":"Dua","year":"2018","journal-title":"Prog Retin Eye Res"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/jcp.v232.4","article-title":"Understanding the pathogenesis of neurotrophic keratitis: the role of corneal nerves","volume":"232","author":"Mastropasqua","year":"2017","journal-title":"J Cell Physiol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1167\/iovs.06-1129","article-title":"The cornea in Sjogren's syndrome: an in vivo confocal study","volume":"48","author":"Villani","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1167\/iovs.06-0127","article-title":"Relation between corneal innervation with confocal microscopy and corneal sensitivity with noncontact esthesiometry in patients with dry eye","volume":"48","author":"Benitez-Del-Castillo","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/S0002-9394(01)00995-3","article-title":"Laser in situ keratomileusis-induced neurotrophic epitheliopathy","volume":"132","author":"Wilson","year":"2001","journal-title":"Am J Ophthalmol"},{"key":"bib43","first-page":"692","article-title":"Neurotrophic factors in the human cornea","volume":"41","author":"You","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1167\/iovs.03-0189","article-title":"Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy","volume":"44","author":"Nagano","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/ICL.0b013e3181f016d0","article-title":"Translational research in corneal epithelial wound healing","volume":"36","author":"Nishida","year":"2010","journal-title":"Eye Contact Lens"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1136\/bjo.2007.130013","article-title":"Open clinical study of eye-drops containing tetrapeptides derived from substance P and insulin-like growth factor-1 for treatment of persistent corneal epithelial defects associated with neurotrophic keratopathy","volume":"92","author":"Yamada","year":"2008","journal-title":"Br J Ophthalmol"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1007\/BF00165937","article-title":"Treatment of persistent epithelial defects in neurotrophic keratitis with epidermal growth factor: a preliminary open study","volume":"230","author":"Daniele","year":"1992","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.ophtha.2018.02.022","article-title":"Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis","volume":"125","author":"Bonini","year":"2018","journal-title":"Ophthalmology"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.exer.2017.06.015","article-title":"PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection","volume":"161","author":"He","year":"2017","journal-title":"Exp Eye Res"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1167\/iovs.15-16755","article-title":"The PEDF neuroprotective domain plus DHA induces corneal nerve regeneration after experimental surgery","volume":"56","author":"He","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.tins.2006.03.005","article-title":"Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors","volume":"29","author":"Bazan","year":"2006","journal-title":"Trends Neurosci"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"18486","DOI":"10.1074\/jbc.M117.801472","article-title":"Defining a mechanistic link between pigment epithelium-derived factor, docosahexaenoic acid, and corneal nerve regeneration","volume":"292","author":"Pham","year":"2017","journal-title":"J Biol Chem"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"3121","DOI":"10.1167\/iovs.05-0241","article-title":"Topical combination of NGF and DHA increases rabbit corneal nerve regeneration after photorefractive keratectomy","volume":"46","author":"Esquenazi","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1167\/iovs.09-3641","article-title":"Neuroprotectin D1 synthesis and corneal nerve regeneration after experimental surgery and treatment with PEDF plus DHA","volume":"51","author":"Cortina","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1080\/13543784.2019.1677605","article-title":"Recent innovations with drugs in clinical trials for neurotrophic keratitis and refractory corneal ulcers","volume":"28","author":"Bremond-Gignac","year":"2019","journal-title":"Expert Opin Investig Drugs"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"e0194345","DOI":"10.1371\/journal.pone.0194345","article-title":"The corneal epitheliotrophic abilities of lyophilized powder form human platelet lysates","volume":"13","author":"Chen","year":"2018","journal-title":"PLoS One"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"e0171008","DOI":"10.1371\/journal.pone.0171008","article-title":"comparison of corneal epitheliotrophic capacities among human platelet lysates and other blood derivatives","volume":"12","author":"Huang","year":"2017","journal-title":"PLoS One"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.clae.2016.06.003","article-title":"Therapeutic outcomes of combined topical autologous serum eye drops with silicone-hydrogel soft contact lenses in the treatment of corneal persistent epithelial defects: a preliminary study","volume":"39","author":"Lee","year":"2016","journal-title":"Cont Lens Anterior Eye"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1097\/ICO.0b013e3181eadb67","article-title":"Comparison of corneal epitheliotrophic capacity among different human blood-derived preparations","volume":"30","author":"Shen","year":"2011","journal-title":"Cornea"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.ajo.2010.03.024","article-title":"The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty","volume":"150","author":"Chen","year":"2010","journal-title":"Am J Ophthalmol"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2772215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:26Z","timestamp":1791927086000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2772215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,22]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,4]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.62.1.23","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1,22]]}}}