Skip to main content

Alterations of epithelial adhesion molecules and basement membrane components in lattice corneal dystrophy (LCD)

Abstract

Background

The aim of the study was to investigate the histopathological and ultrastructural correlate of delayed epithelial healing in eyes with lattice corneal dystrophy (LCD).

Materials and Methods

Corneal buttons from 4 patients with LCD (two with subepithelial, two with stromal amyloid deposits) and 2 control corneas were examined. Cell-matrix adhesion molecules and basement membrane components of the corneal epithelium were analyzed by immunohistochemistry and hemidesmosomes between epithelium and stroma were quantified by transmission electron microscopy (TEM).

Results

By TEM well-developed hemidesmosomes anchored the basal epithelial cells to the underlying basement membrane in all normal and LCD corneas. Hemidesmosome density was not significantly different in subepithelial (224.7 ± 34.1/100 µm) and stromal (234.3 ± 36.3/100 µm) LCD compared to controls (241.3 ± 26.8/100 µm). The basement membrane was interrupted in subepithelial, but continous in stromal LCD. Integrin α6 and ß4 staining formed a continous line along the basal surface of the corneal epithelium in control corneas, whereas it appeared discontinous and patchy both in subepithelial and stromal forms of LCD. Staining for αV integrin showed irregular staining patterns, i.e. enhanced labelling intensity in subepithelial and interrupted pattern in stromal LCD, respectively. Integrins α3, ß1, ß2, and ß5, dystroglycan, and plectin were not markedly different in dystrophic corneas. Type VII collagen showed a discontinuous staining in subepithelial forms of LCD. In stromal forms of LCD, type VII collagen staining occurred in additional patches underneath the epithelial basement membrane zone. Type XVII collagen staining was reduced in subepithelial LCD. Laminin-1, laminin-5 and laminin γ2 showed variable irregular staining patterns in dystrophic corneas with focal interruptions, focal thickenings, and reduplications of basement membrane. Some irregularities in corneas with subepithelial amyloid were observed for collagen types IV, V, and XVIII, laminin α1, α3, and γ1, nidogen-1 and -2, perlecan, fibrillin-1.

Conclusions

Immunohistochemical and electron microscopic evidence of structural alterations was found in LCD compared to normal corneas concerning cell-matrix adhesion molecules and basement membrane components. These alterations were more pronounced in dystrophic corneas with subepithelial amyloid deposits than in those with stromal deposits. Histopathological findings may correspond to reduced cell-matrix interactions and partly explain delayed epithelial healing in patients with lattice corneal dystrophy.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Weiss JS, Moller H, Lisch W, Kinoshita S, Aldave A, Belin MW, Busin M, Munier F, Seitz B, Sutphin J, Bredrup C, Mannis M, Rapuano C, Van Rij G, Kim EK, Klinthworth GK (2008) The IC3D Classification of Corneal Dystrophies. Cornea 27(Suppl 2):S1–S42

    PubMed  Article  Google Scholar 

  2. Süveges I (1967) Contribution to the histochemistry of lattice dystrophy of the cornea. Am J Ophthalmol 64:761–766

    PubMed  Google Scholar 

  3. Das S, Langenbucher A, Seitz B (2005) Delayed healing of corneal epithelium after phototherapeutic keratectomy for lattice dystrophy. Cornea 24:283–287, doi:10.1097/01.ico.0000138853.26332.55

    PubMed  Article  Google Scholar 

  4. Foerster CG, Langenbucher A, Cursiefen C, Kruse FE, Seitz B (2007) Delayed epithelial healing after keratoplasty for lattice corneal dystrophy. Cornea 26:1182–1183

    PubMed  Article  Google Scholar 

  5. Gipson IK (1992) Adhesive mechanisms of the corneal epithelium. Acta Ophthalmol Suppl 202:13–17

    PubMed  Article  Google Scholar 

  6. Päällysaho T, Tervo K, Tervo T, van Setten GB, Virtanen I (1992) Distribution of integrins alpha 6 and beta 4 in the rabbit corneal epithelium after anterior keratectomy. Cornea 11:523–528, doi:10.1097/00003226-199211000-00007

    PubMed  Article  Google Scholar 

  7. Resch MD, Schlötzer-Schrehardt U, Hofmann-Rummelt C, Sauer R, Kruse FE, Seitz B (2006) Adhesion structures of amniotic membranes integrated into human corneas. Invest Ophthalmol Vis Sci 47:1853–1861, doi:10.1167/iovs.05-0983

    PubMed  Article  Google Scholar 

  8. Das S, Langenbucher A, Seitz B (2005) Excimer laser phototherapeutic keratectomy for granular and lattice corneal dystrophy: a comparative study. J Refract Surg 21:727–731

    PubMed  Google Scholar 

  9. Das S, Seitz B (2008) Recurrent corneal erosion syndrome. Surv Ophthalmol 53:3–15, doi:10.1016/j.survophthal.2007.10.011

    PubMed  Article  Google Scholar 

  10. Tuori A, Uusitalo H, Burgeson RE, Terttunen J, Virtanen I (1996) The immunohistochemical composition of the human corneal basement membrane. Cornea 15:286–294, doi:10.1097/00003226-199605000-00010

    PubMed  Article  CAS  Google Scholar 

  11. Tervo K, Tervo T, van Setten GB, Virtanen I (1991) Integrins in human corneal epithelium. Cornea 10:461–465, doi:10.1097/00003226-199111000-00001

    PubMed  Article  CAS  Google Scholar 

  12. Päällysaho T, Tervo T, Virtanen I, Tervo K (1992) Integrins in the normal and healing corneal epithelium. Acta Ophthalmol Suppl 202:22–25

    PubMed  Article  Google Scholar 

  13. Gipson IK, Spurr-Michaud S, Tisdale A, Elwell J, Stepp MA (1993) Redistribution of the hemidesmosome components alpha 6 beta 4 integrin and bullous pemphigoid antigens during epithelial wound healing. Exp Cell Res 207:86–98, doi:10.1006/excr.1993.1166

    PubMed  Article  CAS  Google Scholar 

  14. Vorkauf W, Vorkauf M, Nölle B, Duncker G (1995) Adhesion molecules in normal and pathological corneas. An immunohistochemical study using monoclonal antibodies. Graefes Arch Clin Exp Ophthalmol 233:209–219, doi:10.1007/BF00183594

    Article  CAS  Google Scholar 

  15. Latvala T, Päällysaho T, Tervo K, Tervo T (1996) Distribution of alpha 6 and beta 4 integrins following epithelial abrasion in the rabbit cornea. Acta Ophthalmol Scand 74:21–25

    PubMed  Article  CAS  Google Scholar 

  16. Fujikawa LS, Foster CS, Gipson IK, Colvin RB (1984) Basement membrane components in healing rabbit corneal epithelial wounds: immunofluorescence and ultrastructural studies. J Cell Biol 98:128–138, doi:10.1083/jcb.98.1.128

    PubMed  Article  CAS  Google Scholar 

  17. Dahlbäck K, Sakai L (1990) Immunohistochemical studies on fibrillin in amyloidosis, lichen ruber planus and porphyria. Acta Derm Venereol 70:275–280

    PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Miklós D. Resch.

Additional information

Data were presented in part at the congress of the German Ophthalmological Society (DOG, 20-23. September 2007, Berlin, Germany).

All authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Resch, M.D., Schlötzer-Schrehardt, U., Hofmann-Rummelt, C. et al. Alterations of epithelial adhesion molecules and basement membrane components in lattice corneal dystrophy (LCD). Graefes Arch Clin Exp Ophthalmol 247, 1081 (2009). https://doi.org/10.1007/s00417-009-1046-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00417-009-1046-1

Keywords

  • Lattice corneal dystrophy
  • Basement membrane
  • Adhesion molecules
  • Hemidesmosome
  • Immunohistochemistry