Protective Effects and Mechanisms of Lactoferrin and HIF-1α on Dry Eye Syndrome in Mice.

Abstract

The objective of this study was to investigate the protective effects and related mechanisms of lactoferrin and HIF-1α on dry eye syndrome (DED) in mice. The expression levels of lactoferrin and HIF-1α in tears of DED patients and normal controls were detected. A DED mouse model received lactoferrin (50 mg/kg dissolved in 2 mL PBS) or DMOG (40 mg/kg dissolved in 2 mL PBS) orally daily for 28 days. DMOG (dimethyloxaloylglycine) is a hypoxia-inducible factor prolyl hydroxylase inhibitor. Various tests conducted in this study were phenol red thread test, corneal fluorescein sodium staining, hematoxylin-eosin (HE) staining, PAS staining of conjunctiva, TUNEL staining, and Western blotting. Compared to normal controls, DED patients showed significantly decreased expression of lactoferrin and increased expression of HIF-1α in tears (P<0.05). Compared to normal mice, DED model mice exhibited significantly decreased tear secretion, goblet cell count, Bcl-2, lactoferrin, and STAT3 protein expression levels, and significantly increased corneal fluorescein sodium staining grade, TUNEL positivity rate, Bax, HIF-1α, p21, and p27 protein expression levels (P<0.05). Treatment with lactoferrin or DMOG significantly increased tear secretion, goblet cell count, Bcl-2, lactoferrin, HIF-1α, and STAT3 protein expression levels, and significantly decreased corneal fluorescein sodium staining grade, TUNEL positivity rate, Bax, p21, and p27 protein expression levels in DED model mice (P<0.05). Normal mice showed normal corneal morphology. Compared to normal mice, DED model mice exhibited rough surface of corneal epithelial cell layer with vacuolated cells and inflammatory cell infiltration. Treatment with lactoferrin or DMOG significantly alleviated corneal lesions in DED model mice. Lactoferrin and HIF-1α exert protective effects on DED in mice.