Sensory nerve regeneration after epithelium wounding in normal and diabetic corneas

References

• Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med 1994;331(21):1428-36
   PubMed Web of Science ®Google Scholar
• Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb Perspect Med 2012;2(11):a007641
   Google Scholar
• Beck-Nielsen H, Groop LC. Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus. J Clin Invest 1994;94(5):1714-21
   PubMed Web of Science ®Google Scholar
• Kahn CR. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 1994;43(8):1066-84
   PubMed Web of Science ®Google Scholar
• Clark CM, Lee DA. Prevention and treatment of the complications of diabetes mellitus. N Engl J Med 1995;332(18):1210-17
   PubMed Web of Science ®Google Scholar
• Cousen P, Cackett P, Bennett H, et al. Tear production and corneal sensitivity in diabetes. J Diabetes Complications 2007;21(6):371-3
   PubMed Web of Science ®Google Scholar
• Saito J, Enoki M, Hara M, et al. Correlation of corneal sensation, but not of basal or reflex tear secretion, with the stage of diabetic retinopathy. Cornea 2003;22(1):15-18
   PubMed Web of Science ®Google Scholar
• Figueroa-Ortiz LC, Jimenez Rodriguez E, Garcia-Ben A, et al. Study of tear function and the conjunctival surface in diabetic patients. Arch Soc Esp Oftalmol 2011;86(4):107-12
   PubMedGoogle Scholar
• Kaji Y. Prevention of diabetic keratopathy. Br J Ophthalmol 2005;89(3):254-5
   PubMed Web of Science ®Google Scholar
• Aiello LP, Gardner TW, King GL, et al. Diabetic retinopathy. Diabetes Care 1998;21(1):143-56
   PubMed Web of Science ®Google Scholar
• Didenko TN, Smoliakova GP, Sorokin EL, Egorov VV. Clinical and pathogenetic features of neurotrophic corneal disorders in diabetes. Vestn Oftalmol 1999;115(6):7-11
   PubMedGoogle Scholar
• Friend J, Thoft RA. The diabetic cornea. Int Ophthalmol Clin 1984;24(4):111-23
   PubMedGoogle Scholar
• Friend J, Ishii Y, Thoft RA. Corneal epithelial changes in diabetic rats. Ophthalmic Res 1982;14(4):269-78
   PubMed Web of Science ®Google Scholar
• Kabosova A, Kramerov AA, Aoki AM, et al. Human diabetic corneas preserve wound healing, basement membrane, integrin and MMP-10 differences from normal corneas in organ culture. Exp Eye Res 2003;77(2):211-17
   PubMed Web of Science ®Google Scholar
• Bikbova G, Oshitari T, Tawada A, et al. Corneal changes in diabetes mellitus. Curr Diabetes Rev 2012;8(4):294-302
   PubMedGoogle Scholar
• Lockwood A, Hope-Ross M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye (Lond) 2006;20(7):837-9
   PubMed Web of Science ®Google Scholar
• Frank RN. Diabetic retinopathy. N Engl J Med 2004;350(1):48-58
   PubMed Web of Science ®Google Scholar
• Rosenberg ME, Tervo TM, Immonen IJ, et al. Corneal structure and sensitivity in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci 2000;41(10):2915-21
   PubMed Web of Science ®Google Scholar
• Taylor HR, Kimsey RA. Corneal epithelial basement membrane changes in diabetes. Invest Ophthalmol Vis Sci 1981;20(4):548-53
   PubMed Web of Science ®Google Scholar
• Azar DT, Spurr MS, Tisdale AS, et al. Altered epithelial-basement membrane interactions in diabetic corneas. Arch Ophthalmol 1992;110(4):537-40
   PubMed Web of Science ®Google Scholar
• McDermott AM, Xiao TL, Kern TS, et al. Non-enzymatic glycation in corneas from normal and diabetic donors and its effects on epithelial cell attachment in vitro. Optometry 2003;74(7):443-52
   PubMedGoogle Scholar
• Friend J, Ishii Y, Thoft RA. Corneal epithelial changes in diabetic rats. Ophthalmic Res 1982;14(4):269-78
   PubMed Web of Science ®Google Scholar
• Quadrado MJ, Popper M, Morgado AM, et al. Diabetes and corneal cell densities in humans by in vivo confocal microscopy. Cornea 2006;25(7):761-8
   PubMed Web of Science ®Google Scholar
• Ljubimov AV, Huang ZS, Huang GH, et al. Human corneal epithelial basement membrane and integrin alterations in diabetes and diabetic retinopathy. J Histochem Cytochem 1998;46(9):1033-42
   PubMed Web of Science ®Google Scholar
• Zagon IS, Sassani JW, McLaughlin PJ. Insulin treatment ameliorates impaired corneal reepithelialization in diabetic rats. Diabetes 2006;55(4):1141-7
   PubMed Web of Science ®Google Scholar
• Xu K, Yu FS. Impaired epithelial wound healing and EGFR signaling pathways in the corneas of diabetic rats. Invest Ophthalmol Vis Sci 2011;52:3301-8
   PubMed Web of Science ®Google Scholar
• Wakuta M, Morishige N, Chikama T, et al. Delayed wound closure and phenotypic changes in corneal epithelium of the spontaneously diabetic Goto-Kakizaki rat. Invest Ophthalmol Vis Sci 2007;48(2):590-6
   PubMed Web of Science ®Google Scholar
• Inoue K, Okugawa K, Amano S, et al. Blinking and superficial punctate keratopathy in patients with diabetes mellitus. Eye 2005;19(4):418-21
   PubMed Web of Science ®Google Scholar
• Rehany U, Ishii Y, Lahav M, Rumelt S. Ultrastructural changes in corneas of diabetic patients: an electron-microscopy study. Cornea 2000;19(4):534-8
   PubMed Web of Science ®Google Scholar
• Yin J, Huang J, Chen C, et al. Corneal complications in streptozocin-induced type I diabetic rats. Invest Ophthalmol Vis Sci 2011;52(9):6589-96
   PubMed Web of Science ®Google Scholar
• Saini J, Khandalavla B. Corneal epithelial fragility in diabetes mellitus. Canadian J Ophthalmol 1995;30:142-6
   PubMed Web of Science ®Google Scholar
• Sato N, Nakamura M, Chikama T, Nishida T. Abnormal deposition of laminin and type IV collagen at corneal epithelial basement membrane during wound healing in diabetic rats. Jpn J Ophthalmol 1999;43(5):343-7
   PubMed Web of Science ®Google Scholar
• Kenney MC, Chwa M, Atilano SR, et al. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Invest Ophthalmol Vis Sci 2005;46(3):823-32
   PubMed Web of Science ®Google Scholar
• Xu KP, Li Y, Ljubimov AV, et al. High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing. Diabetes 2009;58(5):1077-85
   PubMed Web of Science ®Google Scholar
• Pflugfelder SC. Is autologous serum a tonic for the ailing corneal epithelium? Am J Ophthalmol 2006;142(2):316-17
   PubMed Web of Science ®Google Scholar
• Brightbill FS, Myers FL, Bresnick GH. Postvitrectomy keratopathy. Am J Ophthalmol 1978;85(5 Pt 1):651-5
   PubMed Web of Science ®Google Scholar
• Fukushi S, Merola LO, Tanaka M, et al. Reepithelialization of denuded corneas in diabetic rats. Exp Eye Res 1980;31(5):611-21
   PubMed Web of Science ®Google Scholar
• Schultz RO, Van Horn DL, Peters MA, et al. Diabetic keratopathy. Trans Am Ophthalmol Soc 1981;79:180-99
   PubMedGoogle Scholar
• Ishibashi F, Kawasaki A, Yamanaka E, et al. Morphometric features of corneal epithelial basal cells, and their relationship with corneal nerve pathology and clinical factors in patients with type 2 diabetes. J Diabetes Investig 2013;4(5):492-501
   Google Scholar
• Chang PY, Carrel H, Huang JS, et al. Decreased density of corneal basal epithelium and subbasal corneal nerve bundle changes in patients with diabetic retinopathy. Am J Ophthalmol 2006;142(3):488-90
   PubMed Web of Science ®Google Scholar
• Watanabe H, Katakami C, Miyata S, Negi A. Corneal disorders in KKAy mouse: a type 2 diabetes model. Jpn J Ophthalmol 2002;46(2):130-9
   PubMed Web of Science ®Google Scholar
• Cai D, Zhu M, Petroll WM, et al. The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium. Am J Pathol 2014;184(10):2662-70
   PubMed Web of Science ®Google Scholar
• Frueh BE, Korner U, Bohnke M. Confocal microscopy of the cornea in patients with diabetes. Klin Monbl Augenheilkd 1995;206(5):317-19
   PubMed Web of Science ®Google Scholar
• Modis LJr, Szalai E, Kertesz K, et al. Evaluation of the corneal endothelium in patients with diabetes mellitus type I and II. Histol Histopathol 2010;25(12):1531-7
   PubMed Web of Science ®Google Scholar
• Roszkowska AM, Tringali CG, Colosi P, et al. Corneal endothelium evaluation in type I and type II diabetes mellitus. Ophthalmologica 1999;213(4):258-61
   PubMed Web of Science ®Google Scholar
• Muller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res 2003;76(5):521-42
   PubMed Web of Science ®Google Scholar
• Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Experimental Eye Res 1994;59(5):597-605
   PubMed Web of Science ®Google Scholar
• Wang F, Gao N, Yin J, Yu FS. Reduced innervation and delayed re-innervation after epithelial wounding in type 2 diabetic Goto-Kakizaki rats. Am J Pathol 2012;181(6):2058-66
   PubMed Web of Science ®Google Scholar
• Millodot M. A review of research on the sensitivity of the cornea. Ophthalmic Physiol Opt 1984;4(4):305-18
   PubMed Web of Science ®Google Scholar
• Dartt DA. Dysfunctional neural regulation of lacrimal gland secretion and its role in the pathogenesis of dry eye syndromes. Ocular Surface 2004;2(2):76-91
   PubMedGoogle Scholar
• Heigle TJ, Pflugfelder SC. Aqueous tear production in patients with neurotrophic keratitis. Cornea 1996;15(2):135-8
   PubMed Web of Science ®Google Scholar
• Nishida T, Chikama T, Sawa M, et al. Differential contributions of impaired corneal sensitivity and reduced tear secretion to corneal epithelial disorders. Jpn J Ophthalmol 2012;56(1):20-5
   PubMed Web of Science ®Google Scholar
• Marfurt CF, Cox J, Deek S, et al. Anatomy of the human corneal innervation. Exp Eye Res 2010;90(4):478-92
   PubMed Web of Science ®Google Scholar
• MacIver MB, Tanelian DL. Free nerve ending terminal morphology is fiber type specific for A delta and C fibers innervating rabbit corneal epithelium. J Neurophysiol 1993;69(5):1779-83
   PubMed Web of Science ®Google Scholar
• Tanelian DL, Beuerman RW. Responses of rabbit corneal nociceptors to mechanical and thermal stimulation. Exp Neurol 1984;84(1):165-78
   PubMed Web of Science ®Google Scholar
• Gallar J, Pozo MA, Tuckett RP, Belmonte C. Response of sensory units with unmyelinated fibres to mechanical, thermal and chemical stimulation of the cat’s cornea. J Physiol 1993;468:609-22
   PubMed Web of Science ®Google Scholar
• Muller LJ, Pels L, Vrensen GF. Ultrastructural organization of human corneal nerves. Invest Ophthalmol Vis Sci 1996;37(4):476-88
   PubMed Web of Science ®Google Scholar
• Muller LJ, Vrensen GF, Pels L, et al. Architecture of human corneal nerves. Invest Ophthalmol Vis Sci 1997;5):985-94
   PubMed Web of Science ®Google Scholar
• Acosta MC, Belmonte C, Gallar J. Sensory experiences in humans and single-unit activity in cats evoked by polymodal stimulation of the cornea. J Physiol 2001;534(Pt. 2):511-25
   PubMed Web of Science ®Google Scholar
• Feng Y, Simpson TL. Nociceptive sensation and sensitivity evoked from human cornea and conjunctiva stimulated by CO2. Invest Ophthalmol Vis Sci 2003;44(2):529-32
   PubMed Web of Science ®Google Scholar
• Al-Aqaba MA, Fares U, Suleman H, et al. Architecture and distribution of human corneal nerves. Br J Ophthalmol 2010;94(6):784-9
   PubMed Web of Science ®Google Scholar
• Abdelkader H, Patel DV, McGhee C, et al. New therapeutic approaches in the treatment of diabetic keratopathy: a review. Clin Experiment Ophthalmol 2011;39(3):259-70
   PubMed Web of Science ®Google Scholar
• Okada Y, Reinach PS, Kitano A, et al. Neurotrophic keratopathy; its pathophysiology and treatment. Histol Histopathol 2010;25(6):771-80
   PubMed Web of Science ®Google Scholar
• Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol 2014;8:571-9
   PubMedGoogle Scholar
• Bonini S, Rama P, Olzi D, et al. Neurotrophic keratitis. Eye 2003;17(8):989-95
   PubMed Web of Science ®Google Scholar
• Ishida N, Rao GN, del Cerro M, et al. Corneal nerve alterations in diabetes mellitus. Arch Ophthalmol 1984;102(9):1380-4
   PubMed Web of Science ®Google Scholar
• Li JY, Mai CK, Hu YH, et al. Experimental study of corneal innervation in diabetic mellitus. J Tongji Med Univ 1995;15(1):38-40
   PubMedGoogle Scholar
• Hosotani H, Ohashi Y, Kinoshita S, et al. Effects of topical aldose reductase inhibitor CT-112 on corneal sensitivity of diabetic rats. Curr Eye Res 1996;15(10):1005-7
   PubMed Web of Science ®Google Scholar
• He J, Bazan HE. Mapping the nerve architecture of diabetic human corneas. Ophthalmology 2012;119(5):956-64
   PubMed Web of Science ®Google Scholar
• Davidson EP, Coppey LJ, Kardon RH, et al. Differences and similarities in development of corneal nerve damage and peripheral neuropathy and in diet-induced obesity and type 2 diabetic rats. Invest Ophthalmol Vis Sci 2014;55(3):1222-30
   PubMed Web of Science ®Google Scholar
• Yorek MS, Obrosov A, Shevalye H, et al. Effect of diet induced obesity or type 1 or type 2 diabetes on corneal nerves and peripheral neuropathy in C57Bl/6J mice. J Peripher Nerv Syst 2015. [Epub ahead of print]
   PubMedGoogle Scholar
• Zhivov A, Winter K, Hovakimyan M, et al. Imaging and quantification of subbasal nerve plexus in healthy volunteers and diabetic patients with or without retinopathy. PLoS One 2013;8(1):e52157
   PubMedGoogle Scholar
• Malik RA, Kallinikos P, Abbott CA, et al. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia 2003;46(5):683-8
   PubMed Web of Science ®Google Scholar
• Kallinikos P, Berhanu M, O’Donnell C, et al. Corneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci 2004;45(2):418-22
   PubMed Web of Science ®Google Scholar
• Midena E, Brugin E, Ghirlando A, et al. Corneal diabetic neuropathy: a confocal microscopy study. J Refract Surg 2006;22(9 Suppl):S1047-52
   PubMed Web of Science ®Google Scholar
• Nitoda E, Kallinikos P, Pallikaris A, et al. Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy. Curr Eye Res 2012;37(10):898-906
   PubMed Web of Science ®Google Scholar
• Edwards K, Pritchard N, Vagenas D, et al. Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study. Clin Exp Optom 2012;95(3):348-54
   PubMed Web of Science ®Google Scholar
• Ziegler D, Papanas N, Zhivov A, et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes 2014;63(7):2454-63
   PubMed Web of Science ®Google Scholar
• Messmer EM, Schmid-Tannwald C, Zapp D, et al. In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus. Graefes Arch Clin Exp Ophthalmol 2010;248(9):1307-12
   PubMed Web of Science ®Google Scholar
• Premkumar LS, Pabbidi RM. Diabetic peripheral neuropathy: role of reactive oxygen and nitrogen species. Cell Biochem Biophys 2013;67(2):373-83
   PubMed Web of Science ®Google Scholar
• Jack M, Wright D. Role of advanced glycation endproducts and glyoxalase I in diabetic peripheral sensory neuropathy. Transl Res 2012;159(5):355-65
   PubMed Web of Science ®Google Scholar
• Dobrowsky RT, Rouen S, Yu C. Altered neurotrophism in diabetic neuropathy: spelunking the caves of peripheral nerve. J Pharmacol Exp Ther 2005;313(2):485-91
   PubMed Web of Science ®Google Scholar
• Sima AA, Kamiya H. Diabetic neuropathy differs in type 1 and type 2 diabetes. Ann N Y Acad Sci 2006;1084:235-49
   PubMed Web of Science ®Google Scholar
• Hossain P, Sachdev A, Malik RA. Early detection of diabetic peripheral neuropathy with corneal confocal microscopy. Lancet 2005;366(9494):1340-3
   PubMed Web of Science ®Google Scholar
• Schultz RO, Peters MA, Sobocinski K, et al. Diabetic keratopathy as a manifestation of peripheral neuropathy. Am J Ophthalmol 1983;96(3):368-71
   PubMed Web of Science ®Google Scholar
• Efron N, The Glenn A. Fry award lecture 2010: Ophthalmic markers of diabetic neuropathy. Optometry Vis Sci 2011;88(6):661-83
   PubMed Web of Science ®Google Scholar
• Lutty GA. Effects of diabetes on the eye. Invest Ophthalmol Vis Sci 2013;54(14):ORSF81-7
   PubMedGoogle Scholar
• Pritchard N, Edwards K, Vagenas D, et al. Corneal sensitivity is related to established measures of diabetic peripheral neuropathy. Clin Exp Optom 2012;95(3):355-61
   PubMed Web of Science ®Google Scholar
• Hertz P, Bril V, Orszag A, et al. Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy. Diabet Med 2011;28(10):1253-60
   PubMed Web of Science ®Google Scholar
• Ahmed A, Bril V, Orszag A, et al. Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study. Diabetes Care 2012;35(4):821-8
   PubMed Web of Science ®Google Scholar
• Sivaskandarajah GA, Halpern EM, Lovblom LE, et al. Structure-function relationship between corneal nerves and conventional small-fiber tests in type 1 diabetes. Diabetes Care 2013;36(9):2748-55
   PubMed Web of Science ®Google Scholar
• Petropoulos IN, Alam U, Fadavi H, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci 2014;55(4):2071-8
   PubMed Web of Science ®Google Scholar
• Mehra S, Tavakoli M, Kallinikos PA, et al. Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes. Diabetes Care 2007;30(10):2608-12
   PubMed Web of Science ®Google Scholar
• Tavakoli M, Mitu-Pretorian M, Petropoulos IN, et al. Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes 2013;62(1):254-60
   PubMed Web of Science ®Google Scholar
• Schulze SD, Sekundo W, Kroll P. Autologous serum for the treatment of corneal epithelial abrasions in diabetic patients undergoing vitrectomy. Am J Ophthalmol 2006;142(2):207-11
   PubMed Web of Science ®Google Scholar
• Shi L, Chen H, Yu X, et al. Advanced glycation end products delay corneal epithelial wound healing through reactive oxygen species generation. Mol Cell Biochem 2013;383(1-2):253-9
   PubMed Web of Science ®Google Scholar
• Wang F, Gao N, Yin J, et al. Reduced innervation and delayed re-innervation after epithelial wounding in type 2 diabetic Goto-Kakizaki rats. Am J Pathol 2012;181(6):2058-66
   PubMed Web of Science ®Google Scholar
• Xu K, Yu FS. Impaired epithelial wound healing and EGFR signaling pathways in the corneas of diabetic rats. Invest Ophthalmol Vis Sci 2011;52(6):3301-8
   PubMed Web of Science ®Google Scholar
• Nakamura M, Kawahara M, Morishige N, et al. Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1. Diabetologia 2003;46(6):839-42
   PubMed Web of Science ®Google Scholar
• Nakamura M, Sato N, Chikama TI, et al. Hyaluronan facilitates corneal epithelial wound healing in diabetic rats. Exp Eye Res 1997;64(6):1043-50
   PubMed Web of Science ®Google Scholar
• Nakamura M, Sato N, Chikama T, et al. Fibronectin facilitates corneal epithelial wound healing in diabetic rats. Exp Eye Res 1997;64(3):355-9
   PubMed Web of Science ®Google Scholar
• Saghizadeh M, Kramerov AA, Tajbakhsh J, et al. Proteinase and growth factor alterations revealed by gene microarray analysis of human diabetic corneas. Invest Ophthalmol Vis Sci 2005;46(10):3604-15
   PubMed Web of Science ®Google Scholar
• Saghizadeh M, Kramerov AA, Yaghoobzadeh Y, et al. Adenovirus-driven overexpression of proteinases in organ-cultured normal human corneas leads to diabetic-like changes. Brain Res Bull 2010;81(2-3):262-72
   PubMed Web of Science ®Google Scholar
• Saghizadeh M, Kramerov AA, Yu FS, et al. Normalization of wound healing and diabetic markers in organ cultured human diabetic corneas by adenoviral delivery of c-Met gene. Invest Ophthalmol Vis Sci 2010;51(4):1970-80
   PubMed Web of Science ®Google Scholar
• Winkler MA, Dib C, Ljubimov AV, et al. Targeting miR-146a to treat delayed wound healing in human diabetic organ-cultured corneas. PLoS ONE 2014;9(12):e114692
   PubMedGoogle Scholar
• Saghizadeh M, Dib CM, Brunken WJ, et al. Normalization of wound healing and stem cell marker patterns in organ-cultured human diabetic corneas by gene therapy of limbal cells. Exp Eye Res 2014;129:66-73
   PubMed Web of Science ®Google Scholar
• Beuerman RW, Schimmelpfennig B. Sensory denervation of the rabbit cornea affects epithelial properties. Exp Neurol 1980;69(1):196-201
   PubMed Web of Science ®Google Scholar
• Gilbard JP, Rossi SR. Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis. Ophthalmology 1990;97(3):308-12
   PubMed Web of Science ®Google Scholar
• Mackie IA. Role of the corneal nerves in destructive disease of the cornea. Trans Ophthalmol Soc UK 1978;98(3):343-7
   PubMedGoogle Scholar
• Araki K, Ohashi Y, Kinoshita S, et al. Epithelial wound healing in the denervated cornea. Curr Eye Res 1994;13(3):203-11
   PubMed Web of Science ®Google Scholar
• Gallar J, Pozo MA, Rebollo I, et al. Effects of capsaicin on corneal wound healing. Invest Ophthalmol Vis Sci 1990;31(10):1968-74
   PubMed Web of Science ®Google Scholar
• Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Exp Eye Res 1994;59(5):597-605
   PubMed Web of Science ®Google Scholar
• Baker KS, Anderson SC, Romanowski EG, et al. Trigeminal ganglion neurons affect corneal epithelial phenotype. Influence on type VII collagen expression in vitro. Invest Ophthalmol Vis Sci 1993;34(1):137-44
   PubMed Web of Science ®Google Scholar
• Kowtharapu BS, Stahnke T, Wree A, et al. Corneal epithelial and neuronal interactions: role in wound healing. Exp Eye Res 2014;125:53-61
   PubMed Web of Science ®Google Scholar
• Chan KY, Haschke RH. Action of a trophic factor(s) from rabbit corneal epithelial culture on dissociated trigeminal neurons. J Neurosci 1981;1(10):1155-62
   PubMed Web of Science ®Google Scholar
• Chan KY, Haschke RH. Isolation and culture of corneal cells and their interactions with dissociated trigeminal neurons. Exp Eye Res 1982;35(2):137-56
   PubMed Web of Science ®Google Scholar
• Emoto I, Beuerman RW. Stimulation of neurite growth by epithelial implants into corneal stroma. Neurosci Lett 1987;82(2):140-4
   PubMed Web of Science ®Google Scholar
• Chen L, Wei RH, Tan DT, et al. Nerve growth factor expression and nerve regeneration in monkey corneas after LASIK. J Refract Surg 2014;30(2):134-9
   PubMed Web of Science ®Google Scholar
• Li Z, Burns AR, Han L, et al. IL-17 and VEGF are necessary for efficient corneal nerve regeneration. Am J Pathol 2011;178(3):1106-16
   PubMed Web of Science ®Google Scholar
• Zhou Q, Chen P, Di G, et al. Ciliary Neurotrophic Factor Promotes the Activation of Corneal Epithelial Stem/Progenitor Cells and Accelerates Corneal Epithelial Wound Healing. Stem Cells 2014;33(5):1566-76
   Web of Science ®Google Scholar
• Reichard M, Hovakimyan M, Guthoff RF, et al. In vivo visualisation of murine corneal nerve fibre regeneration in response to ciliary neurotrophic factor. Exp Eye Res 2014;120:20-7
   PubMed Web of Science ®Google Scholar
• Sarkar J, Chaudhary S, Jassim SH, et al. CD11b+GR1+ myeloid cells secrete NGF and promote trigeminal ganglion neurite growth: implications for corneal nerve regeneration. Invest Ophthalmol Vis Sci 2013;54(9):5920-36
   PubMed Web of Science ®Google Scholar
• Saghizadeh M, Soleymani S, Harounian A, et al. Alterations of epithelial stem cell marker patterns in human diabetic corneas and effects of c-met gene therapy. Mol Vis 2011;17:2177-90
   PubMed Web of Science ®Google Scholar
• Yamada N, Matsuda R, Morishige N, et al. 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. Br J Ophthalmol 2008;92(7):896-900
   PubMed Web of Science ®Google Scholar
• Nagano T, Nakamura M, Nakata K, et al. Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy. Invest Ophthalmol Vis Sci 2003;44(9):3810-15
   PubMed Web of Science ®Google Scholar
• Nakamura M, Kawahara M, Nakata K, et al. Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicin-induced neurotrophic keratopathy. Invest Ophthalmol Vis Sci 2003;44(7):2937-40
   PubMed Web of Science ®Google Scholar
• Murphy CJ, Marfurt CF, McDermott A, et al. Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1. Invest Ophthalmol Vis Sci 2001;42(10):2252-61
   PubMed Web of Science ®Google Scholar
• Denis P, Fardin V, Nordmann JP, et al. Localization and characterization of substance P binding sites in rat and rabbit eyes. Invest Ophthalmol Vis Sci 1991;32(6):1894-902
   PubMed Web of Science ®Google Scholar
• Nakamura M, Ofuji K, Chikama T, et al. The NK1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1. Br J Pharmacol 1997;120(4):547-52
   PubMed Web of Science ®Google Scholar
• Reid TW, Murphy CJ, Iwahashi CK, et al. Stimulation of epithelial cell growth by the neuropeptide substance P. J Cell Biochem 1993;52(4):476-85
   PubMed Web of Science ®Google Scholar
• Nishida T, Nakamura M, Ofuji K, et al. Synergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea. J Cell Physiol 1996;169(1):159-66
   PubMed Web of Science ®Google Scholar
• Yamada N, Yanai R, Kawamoto K, et al. Promotion of corneal epithelial wound healing by a tetrapeptide (SSSR) derived from IGF-1. Invest Ophthalmol Vis Sci 2006;47(8):3286-92
   PubMed Web of Science ®Google Scholar
• Yamada N, Yanai R, Nakamura M, et al. Role of the C domain of IGFs in synergistic promotion, with a substance P-derived peptide, of rabbit corneal epithelial wound healing. Invest Ophthalmol Vis Sci 2004;45(4):1125-31
   PubMed Web of Science ®Google Scholar
• Nakamura M, Kawahara M, Nakata K, et al. Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicin-induced neurotrophic keratopathy. Invest Ophthalmol Vis Sci 2003;44(7):2937-40
   PubMed Web of Science ®Google Scholar
• Nakamura M, Nishida T, Ofuji K, et al. Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea. Exp Eye Res 1997;65(3):321-9
   PubMed Web of Science ®Google Scholar
• Nakamura M, Ofuji K, Chikama T, et al. Combined effects of substance P and insulin-like growth factor-1 on corneal epithelial wound closure of rabbit in vivo. Curr Eye Res 1997;16(3):275-8
   PubMed Web of Science ®Google Scholar
• Brown SM, Lamberts DW, Reid TW, et al. Neurotrophic and anhidrotic keratopathy treated with substance P and insulinlike growth factor 1. Arch Ophthalmol 1997;115(7):926-7
   PubMed Web of Science ®Google Scholar
• Chikama T, Fukuda K, Morishige N, et al. Treatment of neurotrophic keratopathy with substance-P-derived peptide (FGLM) and insulin-like growth factor I. Lancet 1998;351(9118):1783-4
   PubMed Web of Science ®Google Scholar
• Morishige N, Komatsubara T, Chikama T, et al. Direct observation of corneal nerve fibres in neurotrophic keratopathy by confocal biomicroscopy. Lancet 1999;354(9190):1613-14
   PubMed Web of Science ®Google Scholar
• Yang L, Di G, Qi X, et al. Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor. Diabetes 2014;63(12):4262-74
   PubMed Web of Science ®Google Scholar
• Jones MA, Marfurt CF. Calcitonin gene-related peptide and corneal innervation: a developmental study in the rat. J Comp Neurol 1991;313(1):132-50
   PubMed Web of Science ®Google Scholar
• Heino P, Oksala O, Luhtala J, et al. Localization of calcitonin gene-related peptide binding sites in the eye of different species. Curr Eye Res 1995;14(9):783-90
   PubMed Web of Science ®Google Scholar
• Mikulec AA, Tanelian DL. CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation. J Ocul Pharmacol Ther 1996;12(4):417-23
   PubMed Web of Science ®Google Scholar
• Ueno H, Ferrari G, Hattori T, et al. Dependence of corneal stem/progenitor cells on ocular surface innervation. Invest Ophthalmol Vis Sci 2012;53(2):867-72
   PubMed Web of Science ®Google Scholar
• Bennett JL, Zeiler SR, Jones KR. Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye. Invest Ophthalmol Vis Sci 1999;40(12):2996-3005
   PubMed Web of Science ®Google Scholar
• You L, Kruse FE, Volcker HE. Neurotrophic factors in the human cornea. Invest Ophthalmol Vis Sci 2000;41(3):692-702
   PubMed Web of Science ®Google Scholar
• Lambiase A, Manni L, Bonini S, et al. Nerve growth factor promotes corneal healing: structural, biochemical, and molecular analyses of rat and human corneas. Invest Ophthalmol Vis Sci 2000;41(5):1063-9
   PubMed Web of Science ®Google Scholar
• Lambiase A, Bonini S, Micera A, et al. Expression of nerve growth factor receptors on the ocular surface in healthy subjects and during manifestation of inflammatory diseases. Invest Ophthalmol Vis Sci 1998;39(7):1272-5
   PubMed Web of Science ®Google Scholar
• Kruse FE, Tseng SC. Growth factors modulate clonal growth and differentiation of cultured rabbit limbal and corneal epithelium. Invest Ophthalmol Vis Sci 1993;34(6):1963-76
   PubMed Web of Science ®Google Scholar
• Murphy CJ, Marfurt CF, McDermott A, et al. Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1. Invest Ophthalmol Vis Sci 2001;42(10):2252-61
   PubMed Web of Science ®Google Scholar
• You L, Ebner S, Kruse FE. Glial cell-derived neurotrophic factor (GDNF)-induced migration and signal transduction in corneal epithelial cells. Invest Ophthalmol Vis Sci 2001;42(11):2496-504
   PubMed Web of Science ®Google Scholar
• Romano MR, Biagioni F, Carrizzo A, et al. Effects of vitamin B12 on the corneal nerve regeneration in rats. Exp Eye Res 2014;120:109-17
   PubMed Web of Science ®Google Scholar
• Pan Z, Fukuoka S, Karagianni N, et al. Vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea. FASEB J 2013;27(7):2756-67
   PubMed Web of Science ®Google Scholar
• Yu CQ, Zhang M, Matis KI, et al. Vascular endothelial growth factor mediates corneal nerve repair. Invest Ophthalmol Vis Sci 2008;49(9):3870-8
   PubMed Web of Science ®Google Scholar
• Cortina MS, He J, Li N, et al. Recovery of corneal sensitivity, calcitonin gene-related peptide-positive nerves, and increased wound healing induced by pigment epithelial-derived factor plus docosahexaenoic acid after experimental surgery. Arch Ophthalmol 2012;130(1):76-83
   PubMed Web of Science ®Google Scholar
• Zagon IS, Sassani JW, Allison G, et al. Conserved expression of the opioid growth factor, [Met5]enkephalin, and the zeta (zeta) opioid receptor in vertebrate cornea. Brain Res 1995;671(1):105-11
   PubMed Web of Science ®Google Scholar
• Zagon IS, Sassani JW, McLaughlin PJ. Opioid growth factor modulates corneal epithelial outgrowth in tissue culture. Am J Physiol 1995;268(4 Pt 2):R942-50
   PubMed Web of Science ®Google Scholar
• Zagon IS, Sassani JW, McLaughlin PJ. Reepithelialization of the human cornea is regulated by endogenous opioids. Invest Ophthalmol Vis Sci 2000;41(1):73-81
   PubMed Web of Science ®Google Scholar
• Zagon IS, Jenkins JB, Sassani JW, et al. Naltrexone, an opioid antagonist, facilitates reepithelialization of the cornea in diabetic rat. Diabetes 2002;51(10):3055-62
   PubMed Web of Science ®Google Scholar
• Zagon IS, Sassani JW, Carroll MA, et al. Topical application of naltrexone facilitates reepithelialization of the cornea in diabetic rabbits. Brain Res Bull 2010;81(2-3):248-55
   PubMed Web of Science ®Google Scholar
• Cisarik-Fredenburg P. Discoveries in research on diabetic keratopathy. Optometry 2001;72(11):691-704
   PubMedGoogle Scholar
• Kinoshita JH, Fukushi S, Kador P, et al. Aldose reductase in diabetic complications of the eye. Metabolism 1979;28(4 Suppl 1):462-9
   PubMed Web of Science ®Google Scholar
• Awata T, Sogo S, Yamagami Y, et al. Effect of an aldose reductase inhibitor, CT-112, on healing of the corneal epithelium in galactose-fed rats. J Ocul Pharmacol 1988;4(3):195-201
   PubMedGoogle Scholar
• Ohashi Y, Matsuda M, Hosotani H, et al. Aldose reductase inhibitor (CT-112) eyedrops for diabetic corneal epitheliopathy. Am J Ophthalmol 1988;105(3):233-8
   PubMed Web of Science ®Google Scholar
• Hosotani H, Ohashi Y, Yamada M, et al. Reversal of abnormal corneal epithelial cell morphologic characteristics and reduced corneal sensitivity in diabetic patients by aldose reductase inhibitor, CT-112. Am J Ophthalmol 1995;119(3):288-94
   PubMed Web of Science ®Google Scholar
• Matsuda M, Awata T, Ohashi Y, et al. The effects of aldose reductase inhibitor on the corneal endothelial morphology in diabetic rats. Curr Eye Res 1987;6(2):391-7
   PubMed Web of Science ®Google Scholar
• Ueno H, Hattori T, Kumagai Y, et al. Alterations in the corneal nerve and stem/progenitor cells in diabetes: preventive effects of insulin-like growth factor-1 treatment. Int J Endocrinol 2014;2014:312401
   PubMedGoogle Scholar
• Saghizadeh M, Epifantseva I, Hemmati DM, et al. Enhanced wound healing, kinase and stem cell marker expression in diabetic organ-cultured human corneas upon MMP-10 and cathepsin F gene silencing. Invest Ophthalmol Vis Sci 2013;54(13):8172-80
   PubMed Web of Science ®Google Scholar
• Nakatsu MN, Gonzalez S, Mei H, et al. Human limbal mesenchymal cells support the growth of human corneal epithelial stem/progenitor cells. Invest Ophthalmol Vis Sci 2014;55(10):6953-9
   PubMed Web of Science ®Google Scholar
• Zickri MB, Ahmad NA, Maadawi ZM, et al. Effect of stem cell therapy on induced diabetic keratopathy in albino rat. Int J Stem Cells 2012;5(1):57-64
   Google Scholar
• Bettahi I, Sun H, Gao N, et al. Genome-wide transcriptional analysis of differentially expressed genes in diabetic, healing corneal epithelial cells: hyperglycemia-suppressed TGFbeta3 expression contributes to the delay of epithelial wound healing in diabetic corneas. Diabetes 2014;63(2):715-27
   PubMed Web of Science ®Google Scholar
• Davidson EP, Coppey LJ, Holmes A, et al. Changes in corneal innervation and sensitivity and acetylcholine-mediated vascular relaxation of the posterior ciliary artery in a type 2 diabetic rat. Invest Ophthalmol Vis Sci 2012;53(3):1182-7
   PubMed Web of Science ®Google Scholar
• Gao N, Yin J, Yoon GS, et al. Dendritic cell-epithelium interplay is a determinant factor for corneal epithelial wound repair. Am J Pathol 2011;179(5):2243-53
   PubMed Web of Science ®Google Scholar
• Leppin K, Behrendt AK, Reichard M, et al. Diabetes mellitus leads to accumulation of dendritic cells and nerve fiber damage of the subbasal nerve plexus in the cornea. Invest Ophthalmol Vis Sci 2014;55(6):3603-15
   PubMed Web of Science ®Google Scholar
• Tavakoli M, Boulton AJ, Efron N, et al. Increased Langerhan cell density and corneal nerve damage in diabetic patients: role of immune mechanisms in human diabetic neuropathy. Cont Lens Anterior Eye 2011;34(1):7-11
   PubMedGoogle Scholar