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Enzymatic Mechanisms in Corneal Ulceration with Specific Reference to Familial Dysautonomia: Potential for Genetic Approaches

  • M. Elizabeth Fini
  • Susan A. Slaugenhaupt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 506)

Abstract

Dry eye syndromes cause pathological changes in the corneal epithelium. These changes can lead to epithelial erosion that often worsens to involve melting of the superficial stroma. In the worst cases, disease can progress to corneal perforation and blindness. Such complications are commonly encountered in the clinic, and they are painful and incapacitating for the patient. The inherited disorder, familial dysautonomia (FD) or Riley-Day syndrome, is a particularly heart-breaking condition that causes a severe dry eye syndrome. This and other factors lead to corneal ulceration in 50% of FD patients, many of them children. A great need exists to develop better therapeutic measures for corneal erosion and ulceration due to FD as well as other etiologies. Recent insight on the role of matrix metalloproteinases (MMPs) should lead to new avenues for treatment of these devastating disorders. New genetic discoveries and technologies offer exciting promise for further advances, as discussed below.

Keywords

Gene Therapy Transduction Efficiency Epithelial Defect Photorefractive Keratectomy Corneal Haze 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Anderson, S.L., R. Coli, I.W. Daly, E.A. Kichula, M.J. Rork, S.A. Volpi, S.A.J. Ekstein, and B.Y.Rubin, Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet. 68:753 (2001).CrossRefPubMedPubMedCentralGoogle Scholar
  2. Axelrod, F.B., Familial dysautonomia and other congenital and sensory autonomic neuropathies, in: Cell and Molecular Biology of Neural Development, LB. Blake, ed., Plenum Press, New York, (1974).Google Scholar
  3. Baker, K.S., S.C. Anderson, E.G. Romanowski, R.A. Thoft, and N. SundarRaj,, Trigeminal ganglion neurons affect corneal epithelial phenotype. Invest Ophthalmol Vis Sci. 34:137 (1993).PubMedGoogle Scholar
  4. Berman, M.B., C.H. Dohlman,, Collagenase inhibitors. Arch Ophthalmol. (Paris) 35:95 (1975).Google Scholar
  5. Berman, M.B., Collagenase and corneal ulceration, in: Collagenase in Normal and Pathological Connective Tissues. D.E. Wooley and J.M. Evanson, ed., John Wiley, Chichester (1980).Google Scholar
  6. Berman, M.B., K. Kenyon, K. Hayashi, and N. L’Hernault,, The pathogenesis of epithelial defects and stromal ulceration, in: The Cornea: Transactions of the World Congress on the Cornea111. D. Cavanagh, ed., Raven Press, New York (1988).Google Scholar
  7. Blumenfeld, A., S.A. Slaugenhaupt, F.B. Axelrod, D.E. Lucente, C. Maayan, C.B. Liebert, L.J. Ozelius, J.A. Trofatter, J.L. Haines, X.O. Breakefield, and J.F. Gusella, Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic analysis. Nat Genet. 4:160 (1993).CrossRefPubMedGoogle Scholar
  8. Blumenfeld, A., S.A. Slaugenhaupt, C.B. Liebert, V. Temper, C. Maayan, S. Gill, D.E. Lucente, M. Idelson, K. MacCormack, M.A. Monahan, J. Mull, M. Leyne, M. Mendillo, T. Schiripo, E. Mishori, E.X.O. Breakefield, F.B. Axelrod, and J.F. Gusella, Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31. Am J Hum Genet. 64:1110 (1999).CrossRefPubMedPubMedCentralGoogle Scholar
  9. Brown, P.D., Clinical trials of a low molecular weight matrix metalloproteinase inhibitor in cancer. Ann NY Acad Sci. 732:217 (1994).CrossRefPubMedGoogle Scholar
  10. Brown, P.D., Synthetic inhibitors of matrix metalloproteinases, in: Matrix Metalloproteinases, W.C. Parks and R.P. Mecham, eds., Academic Press, NY (1998).Google Scholar
  11. Cavanagh, H.D., and A.M. Colley, The molecular basis of neurotrophic keratitis. Acta Ophthalmol Suppl. 192:115(1989).PubMedGoogle Scholar
  12. Cintron, C, C.L. Kublin,, Regeneration of corneal tissue. Dev Biol. 61:346 (1977).CrossRefPubMedGoogle Scholar
  13. Cintron, C, L.C. Hassinger, C.L. Kublin, and D.J. Cannon,, Biochemical and ultrastuctural changes in collagen during corneal wound healing. J Ultrastruct Res. 65:13 (1978).CrossRefPubMedGoogle Scholar
  14. Cionni, R.J., C. Katakami, J.B. Labrich, and W.-Y. Kao,, Collagen metabolism following corneal laceration in rabbits. Curr Eye Res. 5:549 (1986).CrossRefPubMedGoogle Scholar
  15. Conn, H., M. Berman, K. Kenyon, R. Langer, and J. Gage,, Stromal vascularization prevents corneal ulceration. Invest Ophthalmol Vis Sci. 19:362–370 (1980).PubMedGoogle Scholar
  16. Dohlman, C.H., H.H. Slansky, P.R. Laibson, M.C. Gnadinger, and J. Rose,. Artificial corneal epithelium in acute alkali burns. Ann Ophthalmol. 357:1(1969)Google Scholar
  17. Dohlman, C.H., The function of the corneal epithelium in health and disease (The Jonas S. Friedenwald Memorial lecture). Invest Ophthalmol Vis Sci. 10:376 (1971).Google Scholar
  18. Falanga, V., Venous ulceration. J Dermatol Surg Oncol. 19:764 (1993)/CrossRefPubMedGoogle Scholar
  19. Fini, M.E., and M.T. Girard, Expression of collagenolytic/gelatinolytic metalloproteinases by normal cornea. Invest Ophthalmol Vis Sci. 31:1779 (1990a).PubMedGoogle Scholar
  20. Fini, M.E., and M.T. Girard,, The pattern of metalloproteinase expression by corneal fibroblasts is altered by passage in cell culture. J Cell Sci. 97(Pt 2):373 (1990b).PubMedGoogle Scholar
  21. Fini, M.E., Cui, T.-Y., Mouldovan, A., Grobelny, D., Galardy, R.E., and Fisher, S.J., An inhibitor of corneal epithelial cell gelatinase. Invest Ophthalmol Vis Sci. 32:151 (1991).Google Scholar
  22. Fini, M.E., W. Parks, W.B. Rinehart, M. Matsubara, M.T. Girard, J.R. Cook, J.A. West-Mays, P.M. Sadow, J.J. Jeffrey, R.E. Burgeson, M. Raizman, R. Kreuger, and J. Zieske,, Role of matrix metalloproteinases in failure to re-epithelialize following corneal injury. Am J Pathol. 149:1287 (1996).PubMedPubMedCentralGoogle Scholar
  23. Fini, M.E., J.R. Cook, R. Mohan, and C.E. Brinckerhoff,, Regulation of matrix metalloproteinase gene expression, in: Matrix Metalloproteinases, W. Parks, and R. Meacham, eds. Academic Press, NY (1998).Google Scholar
  24. Foster, CS., R.P. Zelt, T. Mai-Phan, and K.R. Kenyon,, Immunosuppression and selective inflammatory cell depletion: studies on a guinea pig model of corneal ulceration after alkali burning. Arch Ophthalmol. 100:1820(1982).CrossRefPubMedGoogle Scholar
  25. Girard, M.T., M. Matsubara, C. Kublin, M. Tessier, C Cintran, and M.E. Fini, Stromal fibroblasts synthesize collagenase and stromelysin during long-term remodeling of repair tissue. J Cell Sci. 104:1001 (1993).PubMedGoogle Scholar
  26. Goldberg, M.F., J.W. Payne, and P.W. Brunt,, Ophthalmologic studies of familial dysautonomia. Arch Ophthalmol. 80:733 (1963).Google Scholar
  27. Gray, R.D., and CA. Paterson,, Application of peptide-based matrix metalloproteinase inhibitors in corneal ulceration. Ann NY Acad Sci. 732:206 (1994).CrossRefPubMedGoogle Scholar
  28. Grillo, U.C., and J. Gross,, Collagenolytic activity during mammalian wound repair. Develop Biol. 15:00 (1967).Google Scholar
  29. Groos, E.B., Neurotrophic keratitis. In: Cornea Volume II: Clinical Diagnosis and Management. J.H. Krachmer, M.J. Mannis, and EJ. Holland eds., Mosby Yearbook, St. Louis (1997).Google Scholar
  30. Gross, J., and CM. Lapiere,, Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci USA. 48:1014 (1968).CrossRefGoogle Scholar
  31. Itoi, M., M. Gnadinger, H. Slasky, H. Freeman, and C. Dohlman,, Collagenase in the cornea. Exp Eye Res. 8:369 (1969).CrossRefPubMedGoogle Scholar
  32. Kenyon, K.R., Berman, M., Rose, J., and Gage, J., Prevention of stromal ulceration in the alkali-burned rabbit cornea by glued-on contact lens: evidence for the role of PMNs in collagen degradation. Invest Ophthalmol Vis Sci. 18:570–587Google Scholar
  33. Kenyon, K.R., Decision making in the therapy of external eye disease: non-infected corneal ulcers. J Ophthalmol 89:44(1982).Google Scholar
  34. Kenyon, K.R., Inflammatory mechanisms in corneal ulceration. Trans Am Ophthalmol Soc. 83:610 (1985).PubMedPubMedCentralGoogle Scholar
  35. Laibson, P.R., Recurrent corneal erosions: diagnosis and management, in: Ophthalmology Annual, RD Reinecke, ed., Raven Press, New York, (1989).Google Scholar
  36. Matsubara, M., M.T. Girard, CL. Kublin, C Cintran, and M.E. Fini,, Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodeling cornea. Develop Biol. 147:425 (1991a).CrossRefPubMedGoogle Scholar
  37. Matsubara, M., J. Zieske, and M.E. Fini,, Mechanism of basement membrane dissolution preceding corneal ulceration. Invest Ophthalmol Vis Sci. 32:92 (1991b).Google Scholar
  38. Moses, M.A., The regulation of neovascularization by matrix metalloproteinases and their inhibitors. Stem Cells. 15:180(1997).Google Scholar
  39. Oikarinen, A., M. Kylmaniemi, H. Autio-Harmainen, P. Autio, P., and T. Salo,, Demonstration of 72-kDa and 92-kDa forms of type IV collagenase in human skin: variable expression in various blistering diseases, induction during re-epithelialization, and decrease by topical glucocorticoids. J Invest Dermatol 101:205(1993).CrossRefPubMedGoogle Scholar
  40. Parks, W.C., and U.I. Sires,, Matrix metalloproteinases and skin biology. Curr Opin Dermatol. 3:240 (1995).Google Scholar
  41. Pfister, R., and N. Burnstein,, The alkali burned cornea: I: epithelial and stromal repair. Exp Eye Res. 23:519 (1976).CrossRefPubMedGoogle Scholar
  42. Robertson, P.B., R.B. Ryel, RE. Taylor, K.W. Shyu, and H.M. Fullmer, H. M.,, Collagenase: localization in polymorphonuclear leukocyte granules in the rabbit. Science. 177:64 (1972).CrossRefPubMedGoogle Scholar
  43. Salo, T., M. Makela, M. Kylmaniemi, H. Autio-Harmainen, and H. Larjava,, Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Invest. 70:176 (1994).PubMedGoogle Scholar
  44. Schultz, G.S., S. Strelow, G.A. Stern,, N. Chegini, M.B. Grant,, R.E. Galardy, D. Grobelny, J.J. Rowsey, K. Stonecipher, V. Parmley, and P.T. Khaw, Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Invest Ophthalmol Vis Sci.33:3325 (1992).PubMedGoogle Scholar
  45. Sigelman, S., and J.S. Friedenwald,, Mitotic and wound-healing activities of the corneal epithelium: effect of sensory denervation. Arch Ophthalmol. 52:46 (1954).CrossRefGoogle Scholar
  46. Slansky, H.H., M.I. Freeman, and M. Itoi,, Collagenolytic activity in bovine corneal epithelium. Arch Ophthalmol. 80:496(1968).CrossRefPubMedGoogle Scholar
  47. Slaugenhaupt, S.A. Blumenfeld, S.P. Gill, M. Leyne, J. Mull,, M.P. Cuajungco, C.B. Liebert, B. Chadwick, M. Idelson, L. Reznik, CM. Robbins, I. Makalowska, M. J. Brownstein,, D. Krappmann, C. Scheidereit, C. Maayan, F.B. Axelrod, and J.F. Gusella,, Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet. 68:598 (2001).CrossRefPubMedPubMedCentralGoogle Scholar
  48. Wagoner, M., and K. Kenyon, Focal points 1985: clinical modules for ophthalmologists. Vol III Module 7: Diagnosis and treatment of non-infected corneal ulcers. 1985)Google Scholar
  49. Woessner, J.F., Jr., 1998, The matrix metalloproteinase family, in: Matrix Metalloproteinases, W.C. Parks and R.P. Mecham, eds., Academic Press, NY (1985).Google Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 2002

Authors and Affiliations

  • M. Elizabeth Fini
    • 1
  • Susan A. Slaugenhaupt
    • 2
    • 3
  1. 1.Vision Research Laboratories, New England Eye CenterTufts University School of Medicine and Tufts Center for Vision ResearchBostonUSA
  2. 2.Molecular Neurogenetics UnitMassachusetts General HospitalCharlestownUSA
  3. 3.Harvard Institute of Human GeneticsHarvard Medical School BostonBostonUSA

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