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


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
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.
Alves
M
M
Laboratory of Clinical Physiopathology, Department of Clinical Medicine, School of Medicine, State University of Campinas (UNICAMP), Campinas, Brazil.
Calegari
V C
VC
Cunha
D A
DA
Saad
M J A
MJ
Velloso
L A
LA
Rocha
E M
EM
D000818:Animals; D015153:Blotting, Western; D003228:Conjunctiva / Q000378:metabolism / Q000503:physiopathology; D003315:Cornea / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015352:Dry Eye Syndromes / Q000503:physiopathology; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013666:Tears / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017127:Glycation End Products, Advanced; D007375:Interleukin-1; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha