Influence of Aging on Tear Film Secretion and NF–kB and Advanced Glycated End–products Expression in Lacrimal Glands of Rats

Abstract

Abstract: : Purpose: Advanced glycation end–products (AGE) induce signaling alterations that lead to inflammation and dysfunction in several tissues. Aging reduces insulin signaling in lacrimal gland (LG). To further understand the impact of aging on LG signaling and insulin secretion, the present study evaluated: (1) the differences in AGE, RAGE (Advanced Glycation End– products Receptor) and NF–kB (Nuclear Factor–kB) expression in LG of aging and control rats and (2) tear film alterations in those groups. Methods: 24 month–old and 2 month–old male Wistar rats were compared. Immunohistochemistry evaluated the expression of AGE, RAGE and NF–kB in LG. Tears volume, insulin, IL–1beta, TNF–alpha and peroxidase were measured in vivo. Static insulin secretion from isolated LG and pancreatic beta–cells were compared in aging and control rats by radioimmunoassay. Results: AGE, RAGE and NF–kB expression were higher in LG and cornea of aging rats. The tear volume was 2.40 ±; 0.25 µl in aging and 3.96 ±; 0.42µl in controls rats (P=0.016). IL–1beta levels in tears were 6.22 ±; 0.15 pg/ml of aging rats and 4.26 ±; 0.18 pg/ml in control rats (P= 0.007). TNF–alpha levels were 239.10 ±; 50.02 pg/ml in tears of aging rats and 57.32 ±; 12.68 pg/ml in control rats (P= 0.05). Peroxidase activity was 0.016 ±; 0.002 min –1 in aging LG and 0.033 ±; 0.006 min –1 in control LG (P=0.02). The insulin levels in the tear film of aging and control rats were similar. Conclusions: Aging induces significant alterations in rat LG structure and secretion. The higher expression of AGEs, RAGE and NF–kB in LG of aging rats suggests that aging influence the signaling process in LG that may be involved in LG and tear film alterations but do not affect insulin secretion in the tear film. These observations may help to explain the mechanisms of LG dysfunctions observed in aging.

Keywords: aging • lacrimal gland • signal transduction