{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:17:35Z","timestamp":1792685855679,"version":"4.5.0"},"reference-count":74,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,9]],"date-time":"2004-10-09T00:00:00Z","timestamp":1097280000000},"content-version":"vor","delay-in-days":4005,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[1993,10,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The sympathetic innervation of the mammalian cornea is thought to play an important role in the regulation of epithelial ion transport, mitogenesis, and wound healing following corneal injuries. Anatomically, the three\u2010dimensional organization and relative density of corneal sympathetic innervation in many species remains inadequately described. In the present study, the sympathetic innervation of five different mammals (guinea pig, rat, mouse, hamster, and human) was studied in corneas sectioned parallel to the main axis of fiber orientation by labeling the fibers immunohistochemically with antiserum against tyrosine hydroxylase and an avidin\u2010biotin\u2010diaminobenzidine technique. The results showed that each species displayed a distinctive pattern and density of tyrosine hydroxylase immunoreactive (TH\u2010IR) corneal innervation that was unique to that species. The overall level of TH\u2010IR innervation was highest in the guinea pig, moderate in the human, hamster, and rat, and lowest in the mouse. In all species examined, TH\u2010IR nerves were most numerous in the corneoscleral limbus where they either formed intimate associations with blood vessels or coursed through the connective tissue matrix apparently unrelated to vascular elements. Other TH\u2010IR nerves entered the cornea proper in radially directed stromal nerve bundles to give rise to subepithelial plexuses of varying complexity. Occasional intraepithelial penetrations were observed in the guinea pig, human, and rat. Removal of the superior cervical ganglion resulted in the total loss of TH\u2010IR staining from guinea pig and hamster corneas and in the substantial but incomplete loss of TH\u2010IR staining from rat and mouse corneas, thus demonstrating their predominantly sympathetic origin. Combined sympathetic and sensory ocular denervation in the rat eliminated almost all corneal and limbal TH\u2010IR immunostaining, thus suggesting a minor TH\u2010IR sensory component in this species. In agreement with this conclusion, small numbers of TH\u2010IR sensory neurons and an abundance of TH\u2010IR fibers were observed in the trigeminal ganglia of the rat and guinea pig. Removal of the rat main ciliary ganglion resulted in the loss of additional TH\u2010IR fibers from the chamber angle and iris, thereby confirming a partial parasympathetic contribution to the rat iridial TH\u2010IR innervation. Following unilateral removal of the superior cervical ganglion in rats and guinea pigs, the contralateral cornea contained increased numbers of TH\u2010IR nerves, suggesting an upregulation of tyrosine hydroxylase (TH) expression in some contralateral axons. In summary, these data have shown pronounced interspecies differences in the organization and density of the mammalian corneal TH\u2010IR innervation that may reflect species\u2010specific variation in the level of sympathetic control over select aspects of corneal physiology. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.903360405","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T04:05:36Z","timestamp":1104552336000},"page":"517-531","source":"Crossref","is-referenced-by-count":72,"title":["Immunohistochemical localization of tyrosine hydroxylase in corneal nerves"],"prefix":"10.1002","volume":"336","author":[{"given":"Carl F.","family":"Marfurt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence C.","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(80)90154-5"},{"key":"e_1_2_1_3_1","first-page":"91","article-title":"Modulation of latency and velocity in corneal epithelial wound healing","volume":"26","author":"Beuerman R. W.","year":"1985","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1523\/JNEUROSCI.05-06-01633.1985","article-title":"Appearance of the noradrenergic markers tyrosine hydroxylase and neuropeptide Y in cholinergic nerves of the iris following sympathectomy","volume":"5","author":"Bj\u00f6rklund H.","year":"1985","journal-title":"J. Neurosci."},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(77)90171-3"},{"key":"e_1_2_1_6_1","first-page":"1075","article-title":"Sensitivity and neural organization of the cat cornea","volume":"30","author":"Chan\u2010Ling T.","year":"1989","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_7_1","first-page":"803","volume-title":"System of Ophthalmology","author":"Duke\u2010Elder S.","year":"1965"},{"key":"e_1_2_1_8_1","first-page":"42","article-title":"Adrenergic nerves to the eye and to related structures in man and in the cynomolgus monkey (Macaca irus)","volume":"5","author":"Ehinger B.","year":"1966","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1966.tb03287.x"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1966.tb03176.x"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00331259"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00324622"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00571785"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1152\/ajplegacy.1944.141.5.689","article-title":"The effects of excitement of epinephrine and of sympathectomy on the mitotic activity of the corneal epithelium in rats","volume":"141","author":"Friedenwald J. S.","year":"1944","journal-title":"Am. J. Physiol."},{"key":"e_1_2_1_15_1","first-page":"412","article-title":"Capsaicin\u2010induced corneal changes associated with sensory denervation in neonatal rat","volume":"31","author":"Fujita S.","year":"1987","journal-title":"Jpn. J. Ophthalmol."},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90475-X"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00561148"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00226054"},{"key":"e_1_2_1_19_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000265309","article-title":"Corneal stroma innervation: A quantitative analysis of distribution","volume":"16","author":"Ishida N.","year":"1984","journal-title":"Ophthalmic Res."},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(84)90116-7"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903130110"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-04-00983.1986"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(90)90250-M"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.11.3526"},{"key":"e_1_2_1_25_1","first-page":"99","volume-title":"Chloride Transport in Biological Membranes","author":"Klyce S. D.","year":"1982"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1977.sp011793"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713688509025145"},{"key":"e_1_2_1_28_1","first-page":"354","article-title":"Distribution ofsympathetic nerves in the rabbit cornea","volume":"27","author":"Klyce S. D.","year":"1986","journal-title":"Invest. Ophthal. Vis. Sci."},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903000303"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00309772"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00313540"},{"key":"e_1_2_1_32_1","first-page":"610","article-title":"Histochemical studies on the adrenergic innervation of the chamber angles and corneas","volume":"74","author":"Kumura H.","year":"1970","journal-title":"Acta Soc. Ophthalmol. Jpn."},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(87)80053-2"},{"key":"e_1_2_1_34_1","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1523\/JNEUROSCI.07-11-03574.1987","article-title":"Catecholaminergic neurons and synapses in adult rat ciliary ganglion","volume":"7","author":"Landis S. C.","year":"1987","journal-title":"J. Neurosci."},{"key":"e_1_2_1_35_1","first-page":"592","article-title":"A histochemical study of the adrenergic and cholinergic innervation of the anterior segment of the rabbit eye","volume":"3","author":"Laties A. M.","year":"1964","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091560403"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.10.3511"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(59)90025-1"},{"key":"e_1_2_1_39_1","first-page":"38","article-title":"Innervation of the cornea of monkeys and the effects of denervation","volume":"31","author":"Lim C.","year":"1976","journal-title":"Br. J. Physiol. Opt."},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092220114"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00218883"},{"key":"e_1_2_1_42_1","first-page":"272","article-title":"A histochemical study on the development of the innervation of rabbit cornea","volume":"23","author":"Lukas Z.","year":"1975","journal-title":"Folia Morphol."},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1965.tb04193.x"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902680202"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)91277-5"},{"key":"e_1_2_1_46_1","first-page":"461","article-title":"Sensory and sympathetic innervation of the mammalian cornea","volume":"30","author":"Marfurt C. F.","year":"1989","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_47_1","first-page":"163","article-title":"Electron microscopic study on the corneal nerve with special reference to its endings","volume":"12","author":"Matsuda H.","year":"1968","journal-title":"Jpn. J. Ophthalmol."},{"key":"e_1_2_1_48_1","first-page":"65","article-title":"The effects of the denervation and stimulation of the sympathetic and trigeminal nerve on the mitotic rate of the corneal epithelium in the rabbit","volume":"1","author":"Mishima S.","year":"1957","journal-title":"J. Ophthalmol."},{"key":"e_1_2_1_49_1","first-page":"112","article-title":"Decreased corneal innervation with sprouting of peripheral sensory fibers associated with chronic keratitis in rats treated at birth with capsaicin","volume":"32","author":"Ogilvy C. S.","year":"1991","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_50_1","first-page":"94","article-title":"A system of atypical catecholaminecontaining nerve fibres in the rat iris present after total superior cervical ganglionectomy","volume":"58","author":"Olson L.","year":"1980","journal-title":"Med. Biol."},{"key":"e_1_2_1_51_1","first-page":"221","article-title":"Effects of chronic sympathetic stimulation on corneal wound healing","volume":"28","author":"Perez E.","year":"1987","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/301241a0"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90506-7"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(82)90092-6"},{"key":"e_1_2_1_55_1","first-page":"351","article-title":"Overall distribution of substance P nerves in the rat cornea and their three\u2010dimensional profiles","volume":"25","author":"Sasaoka A.","year":"1984","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_56_1","first-page":"14","article-title":"Nerve structures in human central corneal epithelium. Graefes Arch","volume":"218","author":"Schimmelpfennig B.","year":"1982","journal-title":"Clin. Exp. Ophthalmol."},{"key":"e_1_2_1_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1954.00920050048005"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01945357"},{"key":"e_1_2_1_59_1","first-page":"207","article-title":"Electron microscopic observations on the corneal epithelium after sensory denervation","volume":"11","author":"Suguira S.","year":"1967","journal-title":"J. Ophthalmol."},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(84)90013-X"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(88)80058-7"},{"key":"e_1_2_1_62_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0006-8993(89)90148-0","article-title":"The allocation of nerve fibres to the anterior eye segment and peripheral ganglia of rats. II. The sympathetic innervation","volume":"494","author":"ten Tusscher M. P.","year":"1980","journal-title":"Brain Res."},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00492350"},{"key":"e_1_2_1_64_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/BF00345656","article-title":"Pre\u2010 and postnatal development of catecholamine\u2010containing and cholinesterase\u2010positive nerves of the rat cornea and iriis","volume":"154","author":"Tervo K.","year":"1978","journal-title":"Anat. Embryol."},{"key":"e_1_2_1_65_1","first-page":"147","article-title":"Adrenergic innervation of the rat corneal epithelium","volume":"15","author":"Tervo T.","year":"1976","journal-title":"Invest. Ophthalmol."},{"key":"e_1_2_1_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1976.tb00420.x"},{"key":"e_1_2_1_67_1","doi-asserted-by":"publisher","DOI":"10.1159\/000145634"},{"key":"e_1_2_1_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091900406"},{"key":"e_1_2_1_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(79)90140-4"},{"key":"e_1_2_1_70_1","first-page":"398","article-title":"Histochemical demonstration of adrenergic nerves in the stroma of human cornea","volume":"28","author":"Toivanen M.","year":"1987","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_1_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90046-5"},{"key":"e_1_2_1_72_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1755-3768.1989.tb07098.x","article-title":"Peptidergic and catecholaminergic fibers in the human corneal epithelium: An immunohistochemical and electron microscopic study","volume":"67","author":"Ueda S.","year":"1989","journal-title":"Acta Ophthalmol."},{"key":"e_1_2_1_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)91519-8"},{"key":"e_1_2_1_74_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713688809033207"},{"key":"e_1_2_1_75_1","first-page":"68","article-title":"Observations on the innervation of the cornea","volume":"85","author":"Zander E.","year":"1951","journal-title":"J. Anat."}],"container-title":["Journal of Comparative Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcne.903360405","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.903360405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T14:49:57Z","timestamp":1698245397000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cne.903360405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,10,22]]},"references-count":74,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1993,10,22]]}},"alternative-id":["10.1002\/cne.903360405"],"URL":"https:\/\/doi.org\/10.1002\/cne.903360405","archive":["Portico"],"relation":{},"ISSN":["0021-9967","1096-9861"],"issn-type":[{"value":"0021-9967","type":"print"},{"value":"1096-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,10,22]]}}}