Vitamin D in tear fluid

Xiaowen Lu, Rodolfo A. Elizondo, Rikke Nielsen, Erik I. Christensen, Jun Yang, Bruce D. Hammock, Mitchell Aaron Watsky

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

PURPOSE. To determine the source(s) of vitamin D in tear fluid and examine the expression of the endocytic proteins and putative vitamin D transporters megalin and cubilin in lacrimal and Harderian glands. METHODS. Wild-type, heterozygous, and vitamin D receptor (VDR) knockout C57BL/6 mice were used, with a subset of knockout mice fed a replenishment diet for some studies. Mouse lacrimal and Harderian glands from each group were used to measure megalin and cubilin by RT-PCR, Western blot, and immunohistochemistry. New Zealand white rabbits were used to collect lacrimal and accessory gland fluid for vitamin D mass spectroscopy measurements. RESULTS. Ten-week-old knockout mice were significantly (P < 0.05) smaller than wild-type mice. Real-time PCR and Western blot showed decreased xpression of megalin and cubilin in select VDR knockout mouse groups. mmunohistochemistry showed apical duct cell megalin staining and weaker megalin staining in VDR knockout mice compared with controls. Vitamin D2 was more prevalent in rabbit lacrimal and accessory gland fluid than vitamin D3, and greater amounts of Vitamin D2 were found in in tear fluid obtained directly from lacrimal and accessory glands as compared with plasma concentrations. CONCLUSIONS. This is the first study to demonstrate the presence of megalin and cubilin in lacrimal and accessory glands responsible for producing tear fluid. The results strengthen the hypothesis that megalin and cubilin are likely involved in the secretory pathway of vitamin D into tear fluid by the duct cells.

Original languageEnglish (US)
Pages (from-to)5880-5887
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number10
DOIs
StatePublished - Jan 1 2015

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Low Density Lipoprotein Receptor-Related Protein-2
Lacrimal Apparatus
Tears
Vitamin D
Knockout Mice
Calcitriol Receptors
Harderian Gland
Ergocalciferols
Western Blotting
Nasolacrimal Duct
Staining and Labeling
Rabbits
Cholecalciferol
Secretory Pathway
Inbred C57BL Mouse
Real-Time Polymerase Chain Reaction
Mass Spectrometry
Immunohistochemistry
intrinsic factor-cobalamin receptor
Diet

Keywords

  • Cubilin
  • Lacrimal gland
  • Megalin
  • Tears
  • Vitamin D

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Lu, X., Elizondo, R. A., Nielsen, R., Christensen, E. I., Yang, J., Hammock, B. D., & Watsky, M. A. (2015). Vitamin D in tear fluid. Investigative Ophthalmology and Visual Science, 56(10), 5880-5887. https://doi.org/10.1167/iovs.15-17177

Vitamin D in tear fluid. / Lu, Xiaowen; Elizondo, Rodolfo A.; Nielsen, Rikke; Christensen, Erik I.; Yang, Jun; Hammock, Bruce D.; Watsky, Mitchell Aaron.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 10, 01.01.2015, p. 5880-5887.

Research output: Contribution to journalArticle

Lu, X, Elizondo, RA, Nielsen, R, Christensen, EI, Yang, J, Hammock, BD & Watsky, MA 2015, 'Vitamin D in tear fluid', Investigative Ophthalmology and Visual Science, vol. 56, no. 10, pp. 5880-5887. https://doi.org/10.1167/iovs.15-17177
Lu X, Elizondo RA, Nielsen R, Christensen EI, Yang J, Hammock BD et al. Vitamin D in tear fluid. Investigative Ophthalmology and Visual Science. 2015 Jan 1;56(10):5880-5887. https://doi.org/10.1167/iovs.15-17177
Lu, Xiaowen ; Elizondo, Rodolfo A. ; Nielsen, Rikke ; Christensen, Erik I. ; Yang, Jun ; Hammock, Bruce D. ; Watsky, Mitchell Aaron. / Vitamin D in tear fluid. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 10. pp. 5880-5887.
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N2 - PURPOSE. To determine the source(s) of vitamin D in tear fluid and examine the expression of the endocytic proteins and putative vitamin D transporters megalin and cubilin in lacrimal and Harderian glands. METHODS. Wild-type, heterozygous, and vitamin D receptor (VDR) knockout C57BL/6 mice were used, with a subset of knockout mice fed a replenishment diet for some studies. Mouse lacrimal and Harderian glands from each group were used to measure megalin and cubilin by RT-PCR, Western blot, and immunohistochemistry. New Zealand white rabbits were used to collect lacrimal and accessory gland fluid for vitamin D mass spectroscopy measurements. RESULTS. Ten-week-old knockout mice were significantly (P < 0.05) smaller than wild-type mice. Real-time PCR and Western blot showed decreased xpression of megalin and cubilin in select VDR knockout mouse groups. mmunohistochemistry showed apical duct cell megalin staining and weaker megalin staining in VDR knockout mice compared with controls. Vitamin D2 was more prevalent in rabbit lacrimal and accessory gland fluid than vitamin D3, and greater amounts of Vitamin D2 were found in in tear fluid obtained directly from lacrimal and accessory glands as compared with plasma concentrations. CONCLUSIONS. This is the first study to demonstrate the presence of megalin and cubilin in lacrimal and accessory glands responsible for producing tear fluid. The results strengthen the hypothesis that megalin and cubilin are likely involved in the secretory pathway of vitamin D into tear fluid by the duct cells.

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