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Yang Liu, Shan Yang; The therapeutic effect of Roxadustat in a mouse model of meibomian gland dysfunction. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1289.
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We recently discovered that meibomian glands (MGs) exist in a relatively low oxygen environment in vivo, and that hypoxia inducible factor 1α (HIF1α) plays a very important role in the regulation of MG function. We hypothesize that Roxadustat (Roxa) could serve as a treatment for MG dysfunction (MGD) by activating the HIF1α pathway in MGs. To test our hypothesis, we used a newly identified MGD animal model--the Apolipoprotein E-deficient (ApoE KO) mouse--in our study. The ApoE KO mice present the clinical and pathological changes seen in MGD patients, and are also characterized by a marked increase in total plasma cholesterol levels.
Sixteen adult male ApoE KO mice were used in this study. Four sex- and age-matched wild type (WT) C57BL/6J mice were used as phenotype controls. The ApoE KO mice were treated with vehicle or Roxa for 12 weeks. Ocular surface and adnexal evaluations, and tear volume and body weight measurements were made before and after Roxa treatment. Mouse eyelids were removed and processed for histology and MG area quantification. MG sections were subjected to MG area quantification, LipidTox staining, and immunostaining for HIF1α and its associated proteins, including glucose transporter 1 (Glut1), carbonic anhydrase 9 (CA9), peroxisome proliferator-activated receptor gamma (PPARγ), and the adhesive protein desmoglein (Dsg). Total serum cholesterol was measured at the end of the treatment. Experiments were approved by the Institutional Animal Care and Use Committee of The Schepens Eye Research Institute and adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Roxa significantly reduced MG dropout, decreased corneal fluorescein staining, and increased the tear volume. Roxa also enhanced HIF1α activation, changed the expression pattern of Glut1, CA9 and PPARγ, and significantly increased the expression of Dsg in the MGs. In addition, Roxa significantly decreased the percentage of weight gain and total serum cholesterol level in these mice.
Roxa may serve as a potential new therapy for the treatment of MGD.
This is a 2021 ARVO Annual Meeting abstract.
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