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Disease relevance of Sclera

  • Latrotoxin receptor (CL1AA) and optimedin were shown to be expressed in the iris and ciliary body, as well as in the ganglion and inner nuclear cell layers of the retina, whereas the rat orthologue of the human HNOEL-iso gene was expressed in the iris and sclera and less actively in the trabecular meshwork, retina, and optic nerve [1].
  • RESULTS: Sixteen (80%) of 20 cases developed severe scleral necrosis that required tectonic surgery after bare sclera pterygium excision with mitomycin C or beta-irradiation [2].
  • The significance of hypertelorism, obliquity of eyes, long palpebral fissures, blue scleras, depressed bridge of nose, and prominent upper vermilion border is discussed [3].
  • Peripapillary atrophy was divided into (1) a central zone (zone Beta) with visible, large choroidal vessels and sclera, and (2) a peripheral zone (zone Alpha) with irregular hyper- and hypopigmentation [4].
  • Synthesis of nitric oxide (NO) was blocked by L-NMMA (200 mg kg-1 b.w., i.v.). PGF2 alpha-IE induced marked hyperemia of the surface structures of the eye (conjunctiva, eye lids, nictitating membrane, anterior sclera), as well as increased blood flow of the anterior uvea [5].

High impact information on Sclera

  • ELISA studies and crossed immunoelectrophoresis demonstrated that purified dermatan sulphate proteoglycans isolated from bovine sclera did not react with these antibodies but that the antibody to cartilage proteoglycan reacted with other molecules extracted from sclera [6].
  • Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG [7].
  • IGF-II mRNA was expressed by the loose mesenchymal orbital tissue as it differentiated to form the sclera, but not in the compact mature sclera or cornea, or in the ectodermally derived retina or skin [8].
  • These data represent the first demonstration of TGF-beta3 expression in the sclera and implicate all three TGF-beta isoforms in the control of scleral remodeling during myopia development [9].
  • Reduced collagen fibril diameter is also observed in the sclera of eyes with high myopia [10].

Chemical compound and disease context of Sclera


Biological context of Sclera

  • The sclera of embryonic (days 10 and 14) and young adult (2-week posthatching chicks) contains distinct binding sites for insulin and for insulin-like growth factor-1 (IGF-1) [15].
  • The insulin binding site in the sclera is specific for insulin since it has a high affinity for insulin and a lower affinity for IGF-1 (IC50 for unlabeled insulin = 0.4 nM; unlabeled IGF-1 = 5.0 nM) [15].
  • At intraocular pressures higher than the systolic arterial blood pressure there was still some accumulation of 2-DG in the intraocular tissues, but no blood flow, which indicates that glucose could diffuse into the eye through the sclera [16].
  • We wanted to determine changes in gene expression in the operated and companion eye following lensectomy, especially for extracellular matrix in the sclera [17].
  • RESULTS: Latanoprost or PhXA34 had no or only a slight effect on the regional blood flow when measured 1, 2 1/2, 3, 4 1/2, and 6 hours after dose administration, with the exception of the anterior sclera, in which a moderate increase in blood flow was detected [18].

Anatomical context of Sclera


Associations of Sclera with chemical compounds

  • These studies demonstrate that the larger dermatan sulfate proteoglycans of sclera and cartilage are chemically unrelated to each other and to the smaller dermatan sulfate proteoglycans isolated from these tissues [20].
  • The distribution of proteoglycans and their association with collagen fibrils were studied in human and rabbit sclera following fixation of tissue in glutaraldehyde containing Cuprolinic Blue, a specific stain for proteoglycans when used in the presence of critical concentrations of electrolytes [24].
  • Chicks were monocularly occluded for 10 days and the DNA, hydroxyproline, and glycosaminoglycan contents of the sclera were compared between the normal and the myopic eyes [25].
  • PURPOSE: The present study was undertaken to determine whether exposure of the sclera to prostaglandin (PG)F(2alpha) or to the PGF(2alpha) analogue latanoprost acid alters mRNA for matrix metalloproteinases [26].
  • Normal pigmented and albino rabbits showed similar levels of gentamicin in the cornea, aqueous, and vitreous; however, the drug was barely detectable in iris, choroid-retina, and sclera of pigmented animals, presumably on account of an interaction with melanin-containing tissues [27].

Gene context of Sclera

  • RESULTS: Normal human uvea, retina, sclera, and conjunctiva constitutively expressed TLR4, MD-2, and CD14 mRNA [28].
  • However, collagen I immunoreactivity in sclera and associated structures was greater in Col1a1(r/r) mice than in Col1a1(+/+) mice [29].
  • Among the eye tissues analyzed, Myoc/Tigr mRNA was detected in the combined tissues of the eye angle, sclera, cornea, retina, and optic nerve head [30].
  • Low levels of Eya2 expression was detected in retina, sclera, and cornea [31].
  • MMP-2 was found in sclera, cornea, choroid, vitreous, RPE and retina but was absent from lens [32].

Analytical, diagnostic and therapeutic context of Sclera


  1. Gene expression profile of the rat eye iridocorneal angle: NEIBank expressed sequence tag analysis. Ahmed, F., Torrado, M., Zinovieva, R.D., Senatorov, V.V., Wistow, G., Tomarev, S.I. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  2. Tectonic corneal lamellar grafting for severe scleral melting after pterygium surgery. Ti, S.E., Tan, D.T. Ophthalmology (2003) [Pubmed]
  3. More on human immunodeficiency virus embryopathy. Iosub, S., Bamji, M., Stone, R.K., Gromisch, D.S., Wasserman, E. Pediatrics (1987) [Pubmed]
  4. Correlation between peripapillary atrophy and optic nerve damage in normal-tension glaucoma. Park, K.H., Tomita, G., Liou, S.Y., Kitazawa, Y. Ophthalmology (1996) [Pubmed]
  5. Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Astin, M., Stjernschantz, J., Selén, G. Exp. Eye Res. (1994) [Pubmed]
  6. Mammalian eyes and associated tissues contain molecules that are immunologically related to cartilage proteoglycan and link protein. Poole, A.R., Pidoux, I., Reiner, A., Cöster, L., Hassell, J.R. J. Cell Biol. (1982) [Pubmed]
  7. Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Adam, M.F., Belmouden, A., Binisti, P., Brézin, A.P., Valtot, F., Béchetoille, A., Dascotte, J.C., Copin, B., Gomez, L., Chaventré, A., Bach, J.F., Garchon, H.J. Hum. Mol. Genet. (1997) [Pubmed]
  8. Insulin-like growth factor II may play a local role in the regulation of ocular size. Cuthbertson, R.A., Beck, F., Senior, P.V., Haralambidis, J., Penschow, J.D., Coghlan, J.P. Development (1989) [Pubmed]
  9. Isoform-specific changes in scleral transforming growth factor-beta expression and the regulation of collagen synthesis during myopia progression. Jobling, A.I., Nguyen, M., Gentle, A., McBrien, N.A. J. Biol. Chem. (2004) [Pubmed]
  10. Collagen gene expression and the altered accumulation of scleral collagen during the development of high myopia. Gentle, A., Liu, Y., Martin, J.E., Conti, G.L., McBrien, N.A. J. Biol. Chem. (2003) [Pubmed]
  11. Intraoperative daunorubicin versus conjunctival autograft in primary pterygium surgery. Dadeya, S., Kamlesh, n.u.l.l., Khurana, C., Fatima, S. Cornea (2002) [Pubmed]
  12. Viability of bacteria in glycerin and ethanol preserved sclera. Dailey, J.R., Rosenwasser, G.O. Journal of refractive and corneal surgery. (1994) [Pubmed]
  13. Histamine in the human eye. Nowak, J.Z., Nawrocki, J. Ophthalmic Res. (1987) [Pubmed]
  14. Retinoic acid increases in the retina of the chick with form deprivation myopia. Seko, Y., Shimizu, M., Tokoro, T. Ophthalmic Res. (1998) [Pubmed]
  15. Insulin and IGF-1 binding in chick sclera. Waldbillig, R.J., Arnold, D.R., Fletcher, R.T., Chader, G.J. Invest. Ophthalmol. Vis. Sci. (1990) [Pubmed]
  16. Blood flow and glucose consumption in the optic nerve, retina and brain: effects of high intraocular pressure. Sperber, G.O., Bill, A. Exp. Eye Res. (1985) [Pubmed]
  17. Neonatal aphakia retards ocular growth and alters scleral gene expression in rhesus monkeys. Tarnuzzer, R.W., Fernandes, A., Iuvone, P.M., Lambert, S.R. Mol. Vis. (2005) [Pubmed]
  18. Effect of latanoprost on regional blood flow and capillary permeability in the monkey eye. Stjernschantz, J., Selén, G., Astin, M., Karlsson, M., Resul, B. Arch. Ophthalmol. (1999) [Pubmed]
  19. cDNA cloning and characterization of a cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase. Chai, X., Zhai, Y., Napoli, J.L. J. Biol. Chem. (1997) [Pubmed]
  20. The dermatan sulfate proteoglycans of bovine sclera and their relationship to those of articular cartilage. An immunological and biochemical study. Cöster, L., Rosenberg, L.C., van der Rest, M., Poole, A.R. J. Biol. Chem. (1987) [Pubmed]
  21. Molecular cloning and tissue distribution of keratocan. Bovine corneal keratan sulfate proteoglycan 37A. Corpuz, L.M., Funderburgh, J.L., Funderburgh, M.L., Bottomley, G.S., Prakash, S., Conrad, G.W. J. Biol. Chem. (1996) [Pubmed]
  22. The determination of the diffusion coefficient of krypton in rabbit ocular tissue. Strang, R. Invest. Ophthalmol. Vis. Sci. (1977) [Pubmed]
  23. Iontophoresis of 5-fluorouracil into the conjunctiva and sclera. Kondo, M., Araie, M. Invest. Ophthalmol. Vis. Sci. (1989) [Pubmed]
  24. The ultrastructural organization of proteoglycans and collagen in human and rabbit scleral matrix. Young, R.D. J. Cell. Sci. (1985) [Pubmed]
  25. Increased aggrecan (cartilage proteoglycan) production in the sclera of myopic chicks. Rada, J.A., Thoft, R.A., Hassell, J.R. Dev. Biol. (1991) [Pubmed]
  26. Prostaglandin FP agonists alter metalloproteinase gene expression in sclera. Weinreb, R.N., Lindsey, J.D., Marchenko, G., Marchenko, N., Angert, M., Strongin, A. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  27. Intravitreal injection of gentamicin in rabbits. Effect of inflammation and pigmentation on half-life and ocular distribution. Kane, A., Barza, M., Baum, J. Invest. Ophthalmol. Vis. Sci. (1981) [Pubmed]
  28. Expression of toll-like receptor 4 and its associated lipopolysaccharide receptor complex by resident antigen-presenting cells in the human uvea. Chang, J.H., McCluskey, P., Wakefield, D. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  29. Ocular hypertension in mice with a targeted type I collagen mutation. Aihara, M., Lindsey, J.D., Weinreb, R.N. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  30. Changes in mRNA levels of the Myoc/Tigr gene in the rat eye after experimental elevation of intraocular pressure or optic nerve transection. Ahmed, F., Torrado, M., Johnson, E., Morrison, J., Tomarev, S.I. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  31. Eyes absent: a gene family found in several metazoan phyla. Duncan, M.K., Kos, L., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Tomarev, S.I. Mamm. Genome (1997) [Pubmed]
  32. Membrane type-1 matrix metalloproteinase in human ocular tissues. Smine, A., Plantner, J.J. Curr. Eye Res. (1997) [Pubmed]
  33. The core proteins of large and small interstitial proteoglycans from various connective tissues form distinct subgroups. Heinegård, D., Björne-Persson, A., Cöster, L., Franzén, A., Gardell, S., Malmström, A., Paulsson, M., Sandfalk, R., Vogel, K. Biochem. J. (1985) [Pubmed]
  34. Detection of prostaglandin EP(1), EP(2), and FP receptor subtypes in human sclera. Anthony, T.L., Lindsey, J.D., Aihara, M., Weinreb, R.N. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  35. Hemodynamic parameters in blood vessels in choroidal melanoma xenografts and rat choroid. Braun, R.D., Abbas, A., Bukhari, S.O., Wilson, W. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  36. Distribution of complement in the sclera. Brawman-Mintzer, O., Mondino, B.J., Mayer, F.J. Invest. Ophthalmol. Vis. Sci. (1989) [Pubmed]
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