Immunohistochemical localization of advanced glycation end products in pinguecula

  • Yuichi Kaji
  • Tetsuro Oshika
  • Shiro Amano
  • Fumiki Okamoto
  • Wakako Koito
  • Seikoh Horiuchi
Laboratory Investigation



Advanced glycation end products (AGEs) are known to be deposited in the target organ of ageing. In addition, the deposition of AGEs accelerate the process of ageing. We investigated the immunohistochemical localization of AGEs in pinguecula, one of the ocular changes related with ageing process.


Surgical specimens of conjunctiva with or without pinguecula were prepared from nine patients, respectively. Immunohistochemical localization of AGEs was investigated using monoclonal antibodies to\({\text{N}}^{{\text{ $ \varepsilon $ }}} \)-(carboxymethyl)lysine, pentosidine, imidazolone, and pyrraline.


Moderate to strong immunoreactivities to AGEs were detected in the subepithelial amorphous deposits of all the surgical specimens with pinguecula. In contrast, no or weak immunoreactivities to AGEs were detected in the surgical specimens without pinguecula.


Pinguecula is an aggregation of AGEs-modified proteins. The presence of pinguecula would be an index of local irradiation of ultraviolet rays and decreased antioxidant activities.


Advanced glycation Pinguecula CML Ageing 


  1. 1.
    Amano S, Kaji Y, Oshika T, Oka T, Machinami R, Nagai R, Horiuchi S (2001) Advanced glycation end products in human optic nerve head. Br J Ophthalmol 85:52–55CrossRefPubMedGoogle Scholar
  2. 2.
    Araki N, Ueno N, Chakrabarti B, Morino Y, Horiuchi S (1992) Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging. J Biol Chem 67:10211–10214Google Scholar
  3. 3.
    Dawczynski J, Franke S, Blum M, Kasper M, Stein G, Strobel J (2002) Advanced glycation end-products in corneas of patients with keratoconus. Graefe Arch Clin Exp Ophthalmol 240:296–301CrossRefGoogle Scholar
  4. 4.
    Hayase F, Nagaraj RH, Miyata S, Njoroge FG, Monnier VM (1989) Aging of proteins: immunological detection of a glucose-derived pyrrole formed during Maillard reaction in vivo. J Biol Chem 264:3758–3764PubMedGoogle Scholar
  5. 5.
    Horiuchi S, Araki N, Morino Y (1991) Immunochemical approach to characterize advanced glycation end products of the Maillard reaction. Evidence for the presence of a common structure. J Biol Chem 266:7329–7332PubMedGoogle Scholar
  6. 6.
    Ishibashi T, Murata T, Hangai M, Nagai R, Horiuchi S, Lopez PF, Hinton DR, Ryan SJ (1998) Advanced glycation end products in age-related macular degeneration. Arch Ophthalmol 116:1629–1632PubMedGoogle Scholar
  7. 7.
    Jono T, Kimura T, Takamatsu J, Nagai R, Miyazaki K, Yuzuriha T, Kitamura T, Horiuchi S (2002) Accumulation of imidazolone, pentosidine and\({\text{N}}^{{\text{ $ \varepsilon $ }}} \)-(carboxymethyl)lysine in hippocampal CA4 pyramidal neurons of aged human brain. Pathol Int 52:563–571CrossRefPubMedGoogle Scholar
  8. 8.
    Kaji Y, Amano S, Usui T, Oshika T, Yamashiro K, Ishida S, Suzuki K, Tanaka S, Adamis AP, Nagai R, Horiuchi S (2000) Advanced glycation end products in diabetic corneas. Investig Ophthalmol Vis Sci 41:362–368Google Scholar
  9. 9.
    Kaji Y, Amano S, Usui T, Oshika T, Yamashiro K, Ishida S, Suzuki K, Tanaka S, Adamis AP, Nagai R, Horiuchi S (2003) Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells. Investig Ophthalmol Vis Sci 44:521–528CrossRefGoogle Scholar
  10. 10.
    Kasper M, Funk RH (2001) Age-related changes in cells and tissues due to advanced glycation end products (AGEs). Arch Gerontol Geriatr 32:233–243CrossRefPubMedGoogle Scholar
  11. 11.
    Kessel L, Moldow B, van Best JA, Sander B (2003) Corneal autofluorescence in relation to permeability of the blood-aqueous barrier in diabetic patients with clinically significant macular edema and in an age-matched control group. Curr Eye Res 26:307–312CrossRefPubMedGoogle Scholar
  12. 12.
    Li ZY, Wallace RN, Streeten BW, Kuntz BL, Dark AJ (1991) Elastic fiber components and protease inhibitors in pinguecula. Investig Ophthalmol Vis Sci 32:1573–1585Google Scholar
  13. 13.
    McDermott AM, Xiao TL, Kern TS, Murphy CJ (2003) Non-enzymatic glycation in corneas from normal and diabetic donors and its effects on epithelial cell attachment in vitro. Optometry 74:443–452PubMedGoogle Scholar
  14. 14.
    Miyata T, Ueda Y, Yamada Y, Izuhara Y, Wada T, Jadoul M, Saito A, Kurokawa K, van Ypersele de Strihou C (1998) Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia. J Am Soc Nephrol 9:2349–2356PubMedGoogle Scholar
  15. 15.
    Mott JD, Khalifah RG, Nagase H, Shield CF, Hudson JK, Hudson BG (1997) Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility. Kidney Int 52:1302–1312PubMedCrossRefGoogle Scholar
  16. 16.
    Perkins ES (1985) The association between pinguecula, sunlight and cataract. Ophthalmic Res 17:325–330PubMedCrossRefGoogle Scholar
  17. 17.
    Sato E, Mori F, Igarashi S, Abiko T, Takeda M, Ishiko S, Yoshida A (2001) Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy. Diabetes Care 24:479–482PubMedCrossRefGoogle Scholar
  18. 18.
    Stitt AW (2001) Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol 85:746–753CrossRefPubMedGoogle Scholar
  19. 19.
    Young JD, Finlay RD (1975) Primary spheroidal degeneration of the cornea in Labrador and northern Newfoundland. Am J Ophthalmol 79:129–134PubMedGoogle Scholar
  20. 20.
    Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, Manogue K, Cerami A (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci U S A 91:4766–4770PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Yuichi Kaji
    • 1
  • Tetsuro Oshika
    • 1
  • Shiro Amano
    • 2
  • Fumiki Okamoto
    • 1
  • Wakako Koito
    • 3
  • Seikoh Horiuchi
    • 3
  1. 1.Department of OphthalmologyTsukuba University Institute of Clinical MedicineTsukubaJapan
  2. 2.Department of OphthalmologyUniversity of Tokyo Graduate School of MedicineTokyoJapan
  3. 3.Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical SciencesKumamoto UniversityKumamotoJapan

Personalised recommendations