Diet-induced obesity leads to pro-inflammatory alterations to the vitreous humour of the eye in a rat model

Abstract

Objective and design: The purpose of this study was to investigate if diet-induced obesity (DIO) and subsequent low-level systemic inflammation would result in local increases in pro-inflammatory mediators in the vitreous humour (VH) of the eyes of rats.

Methods: Sixteen male Sprague-Dawley rats were fed a high-fat/high-sucrose (n = 9) or chow control-diet (n = 7) for 12-weeks. RT-qPCR was conducted on RNA from VH cells and a 27-plex Luminex^® Assay was conducted on VH fluid and serum.

Results: Increased protein levels for IL-1β, IL-6, and IL-18 in both serum and VH fluid were observed. VH protein levels for IL-13 and IL-17 were also increased. All mediators significantly increased in VH fluid were also positively correlated with percent body fat. Increased mRNA levels in VH cells for an oxidative stress molecule were accompanied by decreased mRNA levels for an antioxidant scavenger, suggesting an antioxidant/oxidant imbalance in the VH with DIO. In addition, decreased mRNA levels for TRAIL, FAS-L and TGF-β, molecules associated with immune privilege, were also significantly depressed.

Conclusions: DIO-related metabolic disturbances disrupt VH homeostasis in a manner that reflects development of a pro-inflammatory environment. Prolonged exposure to such an environment may lead to overt pathologies with compromised eye function.

Keywords: Antioxidant defense; Chronic inflammation; NLRP3 inflammasome; Obesity; Rat; Vitreous humour.