Blueberry Stem Extract Prevents Lacrimal Hyposecretion in Non-obese Diabetic Mice via Activation of AMPK

In Vivo. 2023 May-Jun;37(3):1003-1015. doi: 10.21873/invivo.13174.


Background/aim: Tears secreted from the lacrimal gland are essential for preserving the ocular surface. Thus, dysfunction of the lacrimal gland in Sjögren's syndrome (SS) can lead to dry eye, resulting in a reduced quality of life. We previously reported that blueberry 'leaf' water extract prevents lacrimal hyposecretion in male non-obese diabetic (NOD) mice in a SS-like model. In this study, we investigated the effect of blueberry 'stem' water extract (BStEx) on lacrimal hyposecretion in NOD mice.

Materials and methods: Male NOD mice were fed 1% BStEx or control (AIN-93G) for 2, 4, or 6 weeks from 4 weeks of age. Pilocarpine-induced tear secretion was measured using a phenol red-impregnated thread. The lacrimal glands were histologically evaluated by HE staining. Inflammatory cytokine levels in the lacrimal glands were measured using ELISA. Immunostaining was performed to examine aquaporin 5 (AQP5) localization. The expression levels of autophagy-related proteins, AQP5, and phosphorylated AMPK were measured using western blotting.

Results: After feeding BStEx to mice for 4 or 6 weeks, tear volume was observed to have increased in the BStEx group compared with that in the control group. There were no significant differences in inflammatory cell infiltration, autophagy-related protein expression, or the localization and expression of AQP5 in the lacrimal glands between the two groups. In contrast, AMPK phosphorylation increased in the BStEx group.

Conclusion: BStEx prevented lacrimal hyposecretion in the SS-like model of male NOD mice, probably by opening tight junctions via the activation of AMPK in lacrimal acinar cells.

Keywords: AMPK phosphorylation; Blueberry Stem; NOD mice; Sjögren’s syndrome; lacrimal gland; tear secretion.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blueberry Plants*
  • Diabetes Mellitus, Experimental* / metabolism
  • Disease Models, Animal
  • Lacrimal Apparatus* / metabolism
  • Lacrimal Apparatus* / pathology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Plant Extracts / pharmacology
  • Quality of Life
  • Sjogren's Syndrome*


  • AMP-Activated Protein Kinases
  • Plant Extracts