Isotretinoin Impairs the Secretory Function of Meibomian Gland Via the PPARγ Signaling Pathway

PURPOSE: To investigate the effects of isotretinoin on the ocular surface and to explore the possible mechanisms. METHODS: Rats were treated with isotretinoin 20 mg/kg/d for five months and tested monthly for tear secretion, fluorescein staining, and infrared photography. After five months of treatment, tissues were harvested for routine staining to evaluate the morphological changes; and real-time polymerase chain reaction, Western blot, and immunohistochemistry to study the expression of associated genes and their products such as forkhead box protein O1 (FoxO1), forkhead box protein O3, peroxisome proliferator–activated receptor γ (PPARγ), adipose differentiation–related protein, elongation of very long chain fatty acids protein 4, fatty acid binding protein 4, matrix metalloproteinase-9, and interleukin-6. RESULTS: Systemically, isotretinoin-treated rats have a significantly lower body weight that controls and apparent skin damage. Locally, although there was no alteration in tear secretion, a significant corneal involvement indicated by increased fluorescein staining scores, and also the contrast of meibomian gland was significantly reduced but no significant atrophy of the acinus was found. In addition, isotretinoin causes a decrease in conjunctival goblet cells. Furthermore, isotretinoin treatment did not cause the upregulation of FoxO1 and inflammation related genes but significantly suppressed the expression of PPARγ pathway. CONCLUSIONS: Isotretinoin does not cause a significant atrophy of the acinus and a significant change of FoxO1 expression in the meibomian gland. Isotretinoin causes meibomian gland dysfunction, affecting meibocyte differentiation and qualitative and quantitative changes in the meibum, through PPARγ pathway.