Meibomian gland and ocular surface changes during high fat diet feeding in mice

Abstract

Purpose : High fat diet (HFD) can lead to metabolic syndrome with characteristic dyslipidemia, abdominal obesity, hypertension, hyperglycemia and insulin resistance. Metabolic syndrome is thought to be linked to Meibomian gland dysfunction (MGD) and MGD is associated with ocular surface changes including dry eye syndrome. The purpose of this study was to determine if HFD alters Meibomian gland structure, corneal epithelial surface organization and tear production in a mouse model of diet-induced obesity.

Methods : Five-week old male C57/BL6 mice were fed a normal diet (ND; 15% kcal fat) or a HFD (42% kcal fat) for 5 or 21 weeks. Cochet-Bonnet aesthesiometry (filament thickness 0.12mm) was performed to evaluate corneal nerve sensitivity. Phenol red thread test was performed for 15 seconds to measure tear volume in awake mice. Corneal epithelial surface microplicae were examined using a TESCAN MIRA 3 scanning electron microscope (SEM). Meibography was performed on excised whole eyelids and Meibomian gland (MG) area was determined using ImageJ software. Data analysis was performed using unpaired two-tailed t-test and expressed as mean± standard deviation.

Results : As found previously, compared to mice fed a ND, mice on a HFD gained more weight at 5 weeks (36.3 ±4.8 g vs 30.0±1.7g, p < 0.05) and at 21 weeks (50.6 ±1.6 vs 41.0±1.8g, p<0.05) and exhibited ≈ 50% reduction in corneal nerve sensitivity where more pressure was needed to elicit a blink response (0.9±0.2 vs 0.6±0.1g/mm², p <0.05) at 5 weeks feeding but not at 21 weeks. Tear production was elevated (≈1.5-fold, p<0.05) after both 5 and 21 weeks on the HFD. SEM imaging suggested fewer corneal epithelial microplicae (consistent with a compromised epithelial surface) after 21 weeks on the HFD. MG hypertrophy was evident on HFD feeding after 5 and 21 weeks (16-18% increase in total Meibomian gland area).

Conclusions : The mouse model of metabolic syndrome shows ocular surface changes (loss of corneal sensitivity) and pathologic changes consistent with a dry eye phenotype and MGD. The increased tear volume seen in the obese mice resembles the watery eyes (epiphora) experienced by many MGD patients.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.