Abstract
Purpose :
In addition to cardiometabolic changes, high fat diet (HFD) feeding causes loss of corneal sensitivity loss and impairs corneal wound healing. Diet reversal (DR) strategies effectively mitigate cardiometabolic effects of HFD and corneal sensitivity loss. Their utility for attenuating the impaired corneal wounding that accompanies HFD feeding, however, remains unclear. This study used a diet-induced obesity mouse model to test the hypothesis that in addition to attenuating corneal sensitivity loss, DR also attenuates impaired corneal wound healing induced by HFD.
Methods :
6-week-old C57BL/6 male mice were fed ad libitum, either normal diet (ND) or HFD for 10 weeks. Some of the HFD-fed mice were then switched to ND (DR group), with the rest continuing their respective feeding regimen for an additional 10 weeks. Mice were weighed weekly. Visceral adiposity was measured by epididymal adipose tissue (eAT) weight and adiposity index and fatty liver by liver weight. Corneal sensitivity was measured every 5 weeks using a Cochet-Bonnet aesthesiometer. At 10 and 20 weeks of feeding, a 2-mm diameter corneal epithelial abrasion wound was created, and wound closure monitored for 30h using sodium fluorescein staining. Data were analyzed with ANOVA. Significance was set at p≤0.05.
Results :
Mice fed HFD-only gained ≥110 % more body weight (p<0.0001) and had ≥50% more visceral adiposity (p<0.005) than mice fed ND-only. Fatty liver was observed in mice fed HFD-only (p<0.001). DR markedly reduced body weight, visceral adiposity, and fatty liver. Corneal sensitivity was significantly reduced in mice fed HFD-only, corresponding to an ≥30% increase in pressure required to elicit a blink compared to mice fed ND-only (p<0.05). DR halted further progression of corneal sensitivity loss. After 5 and 10 weeks of DR, there was no difference in corneal sensitivity between DR group and age-matched ND group. At both 10 and 20 weeks of feeding, corneal wound closure was delayed (~6h) in mice fed HFD-only (p<0.002). DR for 10 weeks returned corneal wound closure to that of age matched fed ND-only.
Conclusions :
The results are consistent with the hypothesis that DR attenuates HFD-induced corneal sensitivity loss and impaired corneal wound healing.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.