Abstract
Purpose :
Obesity has been shown to associate with early changes in retinal function. We recently showed that spontaneous oscillations can be detected by non-evoked electroretinogram (ERG) and that this activity help predict obesity. Moreover, a null mutation for the transient receptor potential vanilloid 4 (TRPV4) cation channel has been shown to mitigate the breakdown of the blood-retinal barrier in a diabetic mouse model, but also to protect from diet-induced obesity. This study tested if the deletion of TRPV4 protects against alterations in the basal activity of the retina associated with obesity.
Methods :
Wild-type (WT) and Trpv4-/- mice (5-7 weeks old) fed with control (30 % lipids, LabDiet Rodents) or cafeteria (60 % lipids, Research diets) diet for 5 weeks were subjected to non-evoked and evoked ERG under both scotopic and photopic conditions. Mice were dark-adapted overnight, and ERG was performed under anesthesia with ketamine-xylazine (7:3). On a weekly basis, body weight and fasting glycemia were measured and both glucose and insulin tolerance tests were performed. Similarly, the amplitude and implicit times of A- and B-waves and oscillatory potentials, as well as the power and peak frequencies of spontaneous oscillations were analyzed. the differences between both pairs of groups in relation to ERG basal activity responses, glycemia and insulin resistance test. ANOVA was used for statistical analysis.
Results :
After 5 weeks of cafeteria diet, WT mice showed hyperphagia, increased body weight and glycemia, insulin resistance, glucose intolerance, no change in evoked ERG responses, but impaired spontaneous activity compared to the control diet-fed group. All recorded parameters were similar between WT and Trpv4-/- mice fed control diet. In contrast, Trpv4-/- mice fed cafeteria diet did not show increased body weight, impaired glucose metabolism, or changes in spontaneous ERG activity.
Conclusions :
TRPV4 per se does not contribute to evoked ERG responses, but its deletion prevents early modifications of spontaneous ERG oscillations induced by cafeteria diet in mice.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.