Abstract
Purpose: :
Obesity is a major public health problem worldwide, and off late, epidemiological studies indicate a preponderance of cataract under obesity conditions. Though, cataract is a multifactorial disorder and various biochemical mechanisms are proposed, the influence of obesity on cataractogenesis has not yet been investigated. A suitable animal model that develops cataract following the onset of obesity will be useful. We investigated the molecular and biochemical basis of predisposition to cataract in a novel obese rat model, WNIN-Ob rat, because 15-20% of WNIN-Ob rats develop cataracts spontaneously by the time they reach 12-15 months of age.
Methods: :
We have analyzed the major biochemical pathways in the normal lens of different age groups of novel obese mutant rat strains- WNIN/Ob and WNIN/GR-Ob, the former with euglycemia and other with impaired glucose tolerance (IGT).
Results: :
Except for the polyol pathway, all other principal pathways of lens remained unaltered. Because of this, sorbitol levels were found to be high in the normal eye lens of WNIN/Ob and WNIN/GR-Ob rats compared to their lean controls from 3-months of age onwards. Increased sorbitol pathway thus seemed to cause oxidative stress in the lens of WNIN/Ob and WNIN/GR-Ob rats resulting in cataract in these animals. These results also indicate a synergistic effect of IGT along with obesity on the activation of sorbitol pathway, putting WNIN/GR-Ob rats at a higher risk of developing cataract.
Conclusions: :
These rat models of metabolic syndrome may thus be valuable tools for investigating obesity-induced cataract and also for developing intervention strategies.
Keywords: cataract • metabolism • pathology: experimental