Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

Motoko Kawashima, Tetsuya Kawakita, Naoko Okada, Yoko Ogawa, Dogru Murat, Shigeru Nakamura, Hideo Nakashima, Shigeto Shimmura, Ken Shinmura, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6. months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

Original languageEnglish
Pages (from-to)724-728
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume397
Issue number4
DOIs
Publication statusPublished - 2010 Jul 1

Keywords

  • Calorie restriction
  • Lacrimal gland
  • Oxidative stress
  • Rat
  • Tear

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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