Abstract
The HNK-1 carbohydrate epitope is part of many cell membrane and extracellular matrix molecules, several of which have been implicated in cell adhesion. It is a versatile tool in eye research. In the human eye this epitope is present in the retina, the optic and ciliary nerves, the ciliary and iris epithelia, the zonular lamella, and the sciera. It is phylogenetically conserved, but the positive cell types vary from species to species. In addition to revealing interspecies differences in the vertebrate retina, the HNK-1 epitope has been used to identify a novel cell type in the eye: the subepithelial matrix cells that reside in the inner connective tissue layer (ICTL) of the ciliary body. Although these cells resemble fibroblasts in ultrastructure, they form a distinct cell population that differs in antigenic profile from fibroblasts in other tissues. The HNK-1 epitope is also associated with the elastic fiber system of the ICTL, which may be produced by the subepithelial matrix cells. It may help to structurally stabilize the ciliary body and the retina. The HNK-1 epitope is also involved in many important eye diseases. The subepithelial matrix cells seem to be susceptible to irrreversible atrophy as a result of glaucoma, thermal injury, and tissue compression. On the other hand, the HNK-1 epitope is found in the extracellular matrix of secondary cataracts and may contribute to its pathogenesis. Finally, this epitope has proved to be useful in identifying deposits of exfoliation material, and in tracing neuroepithelial derivatives in developmental anomalies and tumors of the eye.
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AboT and Batch CM: A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029, 1981.
AndoI and TamakiK: HNK-1 antibody reacts with peripheral nerves and sweat glands in the skin. Br J Dermatol 113:175–178,1985.
Apple DJ, Mamalis N, Olson RJ and Kincaid MC: Intraocular lenses. Evolution, designs, complications, and pathology. Williams & Wilkins, USA, 327–334, 1989.
Ariga T, Kohriyama T, FreddoL, et al: Characterization of sulfated glucuronic acid containing glycolipids reacting with IgM M-proteins in patients with neuropathy. J Biol Chem 262:848–853, 1987.
Arimatsu Y Naegele JR and Barnstable CJ: Molecular markers of neuronal subpopulations in layers 4, 5, and 6 of cat primary visual cortex. J Neurosci 7:1250–1263, 1987.
Bronner-FraserM: Perturbation of cranial neural crest migration by the HNK-1 antibody. Dev Biol 123:321–331, 1987.
Bunn PA Jr. Linnoila I, Minna JD, et al: Small cell lung cancer, endocrine cells of the fetal bronchus, and other neuroendocrine cells express the Leu-7 antigenic determinant present on natural killer cells. Blood 65:764–768, 1985.
Chou DKH, llyas AA, Evans JE, et al: Structure of sulfated glucuronyl glycolipids in the nervous system reacting with HNK-1 antibody and some IgM paraproteins in neuropathy. J Biol Chem 261:11717–11725, 1986.
Dow KE, Mirski SEL, Roder JC and Riopelle RJ: Neuronal proteoglycans: biosynthesis and functional interaction with neurons in vitro. J Neurosci 8:3278–3289, 1988.
Eagle RC, Font RL and Fine BS: The basement membrane exfoliation syndrome. Arch Ophthalmol 97:510–515, 1979.
Effrench-Constant C, Miller RH, KruseJ, et al: Molecular specialization of astrocyte processes at nodes of Ranvier in rat optic nerve. J Cell Biol 102:844–852, 1986.
Hall H, Liu L, SchahnerM and SchmitzB: The L2/HNK-1 carbohydrate mediates adhesion of neural cells to laminin. Eur J Neurosci 5:34–42, 1993.
Hall H, VorherrT and SchachnerM: Characterization of a 21 amino acid peptide sequence of the laminin G2 domain that is involved in HNK-1 carbohydrate binding and cell adhesion. Glycobiology 5:435–441, 1995.
Hietanen J, Uusitalo M, TarkkanenA and KiveläT: Lectin and immunohistochemical comparison of glycoconjugates in the conjunctiva of patients with and without exfoliation syndrome. Br J Ophthalmol 79:467–472, 1995.
Hogan MJ, Alvarado JA and Weddel JE: Histology of the human eye. An atlas and textbook. WB Saunders, Philadelphia, PA, 260–319, 1971.
Ilyas AA, Dobersen MJ, Willison HJ and Quarks RH: Mouse monoclonal and rabbit polyclonal antibodies prepared to human myelin-associated glycoproteins also react with glycosphingolipids of peripheral nerve. J Neuroimmunol 12:99–106, 1986.
Inuzuka T, Quarles RH, Noronha AB, Dobersen MJ and Brady RO: A human lymphocyte antigen is shared with a group of glycoproteins in peripheral nerve. Neurosci Lett 51:105–111, 1984.
Keilhauer G, FaissnerA and SchachnerM: Differential inhibition of neurone-neurone, neurone-astrocyte and astrocyte-astrocyte adhesion by L1, L2 and N-CAM antibodies. Nature 316:728–730, 1985.
KiveläT: Expression of the HNK-1 carbohydrate epitope in human retina and retinoblastoma. An immunohistochemical study with the anti-Leu-7 monoclonal antibody. Virchows Arch A Pathol Anat Histopathol 410:139–146, 1986.
KiveläT, HietanenJ and UusitaloM: Exfoliation syndrome in one eye only - is it truly unilateral? Klin Monatsbl Augenheilkd 206:Suppl 2:5, 1995.
Kivelä T, Kauniskangas L, MiettinenP and TarkkanenA: Glioneuroma associated with colobomatous dysplasia of the anterior uvea and retina. A case simulating medulloepithelioma. Ophthalmol 96:1799–1808, 1989.
Kivelä T, Merenmics L, IlveskoskiI and TarkkanenA: Congenital intraocular teratoma. Ophthalmol 100:782–791, 1993.
Kivelä T Puska P, Raitta C, Immonen I and TarkkanenA: Clinically successful contact transcleral krypton laser cyclopho- tocoagulation. Arch Ophthalmol 113:1447–1453, 1995.
Kivelä T SalonenR and PaetauA: Hydrolethalus: a midline malformation syndrome with optic nerve coloboma and hypoplasia. Acta Neuropathol 91:511–518, 1996.
KiveläT and TarkkanenA: Recurrent medulloepithelioma of the ciliary body. Immunohistochemical characteristics. Ophthalmol 95:1565–1575, 1988.
Konstas AG, Marshall GE and Lee WR: Immunogold localisation of laminin in normal and exfoliative iris. Br J Ophthalmol 74:450–457, 1990.
Kruse J, Keilhauer G, FaissnerA, et al: The Jl glycoprotein - a novel nervous system cell adhesion molecule of the L2/HNK- 1 family. Nature 316:146–148, 1985.
Kruse J, Mailhammer R, WerneckeH, et al: Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibody L2 and HNK-1. Nature 311:153–155, 1984.
Künemund V Jungalwala FB, FischerG, et al: The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions. J Cell Biol 106:213–223, 1988.
Lauweryns JM and van Ranst L: Leu-7 immunoreactivity in human, monkey, and pig bronchopulmonary neuroepithelial bodies and neuroendocrine cells. J Histochem Cytochem 35:687–691, 1987.
Li ZY, Streeten BW and Wallace RN: Association of elastin with pseudoexfoliative material: an immunoelectron microscopic study. Curr Eye Res 7:1163–1172, 1988.
Lipinski M, Braham K, Caillaud JM, et al: HNK-1 antibody detects an antigen expressed on neuroectodermal cells. J Exp Med 158:1775–1780, 1983.
Loveless RW, Floyd-O’Sullivan G, Raynes JG, et al: Human serum amyloid P is a multispecific adhesive protein whose ligands include 6-phosphorylated mannose and the 3-sulphated saccharides galactose, N-acetylgalactosamine and glucuronic acid. EMBOJ 11:813–819, 1992.
Margolis RK, Ripellino JA, GoossenB, et al: Occurrence of the HNK-1 epitope (3-sulfoglucuronic acid) in PC 12 pheocromo- cytoma cells, chromaffin granule membranes, and chondroitin sulfate proteoglycans. Biochem Biophys Res Commun 145:1142–1148, 1987.
Marshall GE, Konstas AGP, AbrahamSand Lee WR: Extracellular matrix in aged human ciliary body: an immunoelectron microscope study. Invest Ophthalmol Vis Sci 33:2546–2560, 1992.
Marshall GE, Konstas AGP and Lee WR: Collagens in ocular tissues. Br J Ophthalmol 77:515–524, 1993.
McGarry RC, Helfand SL, Quarles RH and Roder JC: Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1. Nature 306:376–378, 1983.
MerkouriE and MatsasR: Monoclonal antibody BM89 recognizes a novel cell surface glycoprotein of the L2/HNK-1 family in the developing mammalian nervous system. Neuroscience 50:53–68, 1992.
Mooy CM, Luyten GPM, De Jong PTVM, et al: Neural cell adhesion molecule distribution in primary and metastatic uveal melanoma. Human Pathol 11:1185–1190, 1995.
Morrison JC and Green WR: Light microscopy of the exfoliation syndrome. Acta Ophthalmol 66:5–27, 1988.
Nobile-Orazio E, Hays AP, LatovN, et al: Specificity of mouse and human monoclonal antibodies to myelin-associated glycoprotein. Neurology 34:1336–1342, 1984.
Perentes E, Herbort CP, Rubinstein LJ, et al: Immunohisto chemical characterization of human retinoblastomas in situ with multiple markers. Am J Ophthalmol 103:647–658, 1987.
Pesheva P, Horwitz AF and SchachnerM: Integrin, the cell surface receptor for fibronectin and laminin, expresses the L2/HNK-1 and L3 carbohydrate structures shared by adhesion molecules. Neurosci Lett 83:303–306, 1987.
Qi Y, Wallace RN, Hoepner JA and Streeten BW: HNK-1 epitopes in normal and pseudoexfoliation (PSX) lens capsules by TEM. Invest Ophthalmol Vis Sci 36:S329, 1995.
RingvoldA: Light and electron microscopy of the wall of iris vessels in eyes with and without exfoliation syndrome (pseudoexfoliation of the lens capsule). Virchows Arch A Pathol Anat Histopathol 349:1–9, 1970.
Riopelle RJ, McGarry RC and Roder JC: Adhesion properties of a neuronal epitope recognized by the monoclonal antibody HNK-1. Brain Res 367:20–25, 1986.
Rittig M, Lütjen-Drecoll E, RauterbergJ, et al: Type-VI collagen in the human iris and ciliary body. Cell Tissue Res 259:305–312, 1990.
SadaghianiB and Vielkind JR: Distribution and migration pathways of HNK-1 -immunoreactive neural crest cells in teleost fish embryos. Development 110:197–209, 1990.
Schlötzer-Schrehardt U, DörflerS and Naumann GOH: Immunohistochemical localization of basement membrane components in pseudoexfoliation material of the lens capsule. Curr Eye Res 11:343–355, 1992.
Schlötzer-Schrehardt U, Endress K and Naumann GOH: Immunohistochemical localization of fibrillin in the anterior segment of pseudoexfoliation eyes. Vis Res 36Suppl:S60, 1996.
Schlötzer-Schrehardt U, KühleM and Naumann GOH: Electron-microscopic identification of pseudoexfoliation mate- rial in extrabulbar tissue. Arch Ophthalmol 109:565–570, 1991.
Schuller-Petrovic S, Gebhart W, LassmannH, et al: A shared antigenic determinant between natural killer cells and nervous tissue. Nature 306:179–181, 1983.
Shioda Y, Nagura H, TsutsumiYet al: Distribution of Leu 7 (HNK-1) antigen in human digestive organs: an immunohistochemical study with monoclonal antibody. Histochem J 16:843–854,1984.
Speaknan JS and GhoshM: The conjunctiva in senile lens exfoliation. Arch Ophthalmol 94:1757–1759, 1976.
Streeten BW: Ciliary body. In: Duane TD, Jaeger EA (eds.). Biomedical Foundations of Ophthalmology. Vol 1, Philadelphia, PA: Harper & Row, ch 13:1–28, 1985.
Streeten BW, Dark AJ, Wallace RN, et al: Pseudoexfoliative fibrillopathy in the skin of patients with ocular pseudoexfoliation. Am J Ophthalmol 110:490–499, 1990.
Streeten BW, Li ZY, Wallace RN, et al: Pseudoexfoliative fibril lopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol 110:1757–1762, 1992.
Tucker GC, Aoyama H, LipinskiM, et al: Identical reactivity of monoclonal antibodies HNK-1 and NC-1: conservation in vertebrates on cells derived from the neural primordium and on some leucocytes. Cell Differ 14:223–230, 1984.
VusitaloM: Immunohistochemical localization of chondroitin sulfate proteoglycan and tenascin in the human eye compared with the HNK-1 epitope. Graefes Arch Clin Exp Ophthalmol 232:657–665, 1994.
UusitaloM: The HNK-1 carbohydrate epitope in the anterior segment of the eye. The inner connective tissue layer of the human ciliary body as a distinct element. Medical Doctoral Thesis. University of Helsinki, 1995. Summary published in Acta Ophthalmol Scand 73:363, 1995.
UusitaloM and KiveläT: Differential distribution of the HNK- 1 carbohydrate epitope in the vertebrate retina. Curr Eye Res13:697–704, 1994.
Uusitalo M and Kivelä T: Cell types of secondary cataract - an immunohistochemical analysis with antibodies to cytoskeletal elements and macrophages. Graefes Arch Clin Exp Ophthalmol, in press.
Uusitalo M and Kivelä T: The HNK-1 epitope in the pseudophakic and aphakic eye and secondary cataract. Acta Ophthalmol, in press.
Uusitalo M, KiveläT and TarkkanenA: Identification of a novel element in the human eye: The inner connective tissue layer of the ciliary body characterized with antibodies to the HNK-1 epitope. Invest Ophthalmol Vis Sci 34:2372–2381, 1993.
Uusitalo M, KiveläT and TarkkanenA: Immunoreactivity of exfoliation material for the cell adhesion-related HNK-1 carbohydrate epitope. Arch Ophthalmol 111:1419–1423, 1993.
Uusitalo M, KiveläT and TarkkanenA: The HNK-1 epitope in the inner connective tissue layer of the human ciliary body in exfoliation syndrome and various types of glaucoma. Graefes Arch Clin Exp Ophthalmol 232:8–15, 1994.
Uusitalo M, Schlötzer-SchrehardtU, et al: Immunoelectron microscopic localization of the HNK-1 epitope in the human ciliary body. Vis Res 36, Suppl:S73, 1996.
VincentM and Thiery J-P: A cell surface marker for neural crest and placodal cells: Further evolution in peripheral and central nervous system. Dev Biol 103:468–481, 1984.
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Uusitalo, M., KivelÄ, T. The HNK-1 carbohydrate epitope and the human eye in health and disease. Pathol. Oncol. Res. 3, 8–14 (1997). https://doi.org/10.1007/BF02893345
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DOI: https://doi.org/10.1007/BF02893345