July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Nutritional and hormonal regulation of lysyl oxidase-like 1 and elastic proteins involved in pseudoexfoliation syndrome/glaucoma
Author Affiliations & Notes
  • Matthias Zenkel
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Daniel Berner
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Ursula Hoja
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Francesca Pasutto
    Institute of Human Genetics, University Erlangen Nuernberg, Erlangen, Germany
  • Friedrich E Kruse
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Ursula Schlotzer-Schrehardt
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Footnotes
    Commercial Relationships   Matthias Zenkel, None; Daniel Berner, None; Ursula Hoja, None; Francesca Pasutto, None; Friedrich Kruse, None; Ursula Schlotzer-Schrehardt, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3513. doi:
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      Matthias Zenkel, Daniel Berner, Ursula Hoja, Francesca Pasutto, Friedrich E Kruse, Ursula Schlotzer-Schrehardt; Nutritional and hormonal regulation of lysyl oxidase-like 1 and elastic proteins involved in pseudoexfoliation syndrome/glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3513.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Besides gene variants in LOXL1 (lysyl oxidase-like 1), dietary factors, such as high coffee consumption and low folate intake, have been shown to constitute non-genetic factors associated with increased risk of pseudoexfoliation (PEX) syndrome and glaucoma. Here, we analyzed the effect of various nutritional and hormonal factors on the expression of LOXL1 and elastic proteins in vitro.

Methods : Cultured human Tenon’s capsule fibroblasts obtained from four normal donors were exposed to folate (0.1-100 µM), caffeine (1-20 mM), vitamin D3 (D3, 0.1-5 µM), 9-cis-retinoic acid (RA, 0.1-10 µM), the LXR agonist TO901317 (TO, 1-50 nM), 17-ß-estradiol (E2, 1-50 nM), and triiodothyronine (T3, 1-50 nM) for 48h. The corresponding nuclear receptors for D3 (VDR), RA (RXRA), TO (LXR), E2 (ESR2), and T3 (THRB) were silenced by siRNA transfection. The mRNA and protein expression of LOXL1, fibrillin-1, and elastin were analyzed using real-time PCR, immunohistochemistry, and Western blot analysis.

Results : Folate, caffeine, D3, RA, and TO were found to regulate both mRNA and protein expression of LOXL1 as well as elastic fiber components in human Tenon’s capsule fibroblasts in a dose dependent manner. As compared to unstimulated control cells, the expression of LOXL1 was significantly upregulated by folate (50 µM, 2.5-fold) and D3 (5 µM, 2-fold), whereas caffeine (10 mM, 2-fold), RA (2 µM, 2.5-fold), and TO (10 nM, 2-fold) reduced its expression (p<0.01). Elastin and fibrillin-1 were upregulated in parallel by folate (2-fold) and D3 (2-fold), and downregulated in response to RA (2.5-fold) (p<0.01). Silencing of the retinoid X receptor (RXRA) and the liver X receptor (LXR) resulted in upregulation of LOXL1, elastin, and fibrillin-1 (2-fold), whereas silencing of the D3 receptor (VDR) resulted in downregulation of LOXL1 and fibrillin-1 (2-fold) (p<0.01). Stimulation with E2 or T3, or silencing of their nuclear receptors had no significant effect on the expression of LOXL1 or elastic components.

Conclusions : The findings indicate that nutritional factors can modulate LOXL1 and elastic protein expression, which in turn increases the risk of genetically predisposed individuals to develop PEX syndrome and glaucoma.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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