Increased expression of advanced glycation end-products and their receptor, and activation of nuclear factor kappa-B in lacrimal glands of diabetic rats

Diabetologia. 2005 Dec;48(12):2675-81. doi: 10.1007/s00125-005-0010-9. Epub 2005 Nov 8.

Abstract

Aims/hypothesis: To assess the involvement of the AGE-specific receptor (AGER, also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF-kappaB) activation in the development of lacrimal gland and tear film dysfunction in diabetes, the present study evaluated: (1) lacrimal gland and tear film alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in ocular tissues of normoglycaemic and diabetic rats.

Materials and methods: Diabetes was induced in male Wistar rats with intravenous streptozotocin. Tear secretion parameters were measured and NFKB expression was evaluated in lacrimal glands of control and diabetic rats by western blot. Immunohistochemistry with confocal microscopy was used to assess AGE, AGER and NFKB expression in lacrimal glands of both groups.

Results: Lacrimal gland weight and tear film volume were lower in diabetic than in control rats (p=0.01 and 0.02, respectively). IL1B and TNF concentrations in tears were higher in diabetic than in control rats (p=0.007 and 0.02, respectively). NFKB protein was identified in rat cornea, conjunctiva and lacrimal glands. AGE, AGER and NFKB expression were greater in lacrimal glands of diabetic than in those of control rats.

Conclusions/interpretation: Diabetes induces significant alterations in rat lacrimal gland structure and secretion. The higher expression of AGE, AGER and NFKB in lacrimal glands of diabetic rats suggests that these factors are involved in signalling and in subsequent inflammatory alterations related to dry eye in diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Conjunctiva / metabolism
  • Conjunctiva / physiopathology
  • Cornea / metabolism
  • Cornea / physiopathology
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dry Eye Syndromes / physiopathology
  • Gene Expression
  • Glycation End Products, Advanced / analysis*
  • Glycation End Products, Advanced / genetics
  • Glycation End Products, Advanced / metabolism
  • Immunohistochemistry
  • Interleukin-1 / metabolism
  • Lacrimal Apparatus / metabolism*
  • Lacrimal Apparatus / physiopathology
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Wistar
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Tears / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Glycation End Products, Advanced
  • Interleukin-1
  • NF-kappa B
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Tumor Necrosis Factor-alpha