September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Expression of CACNA1A in Patients with Pseudoexfoliation Syndrome
Author Affiliations & Notes
  • Matthias Zenkel
    Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Francesca Pasutto
    Human Genetics, University Erlangen Nuernberg, Erlangen, Germany
  • Antonio Bergua
    Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Panah Liravi
    Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Steffen Uebe
    Human Genetics, University Erlangen Nuernberg, Erlangen, Germany
  • Fulvia Ortolani
    Human Genetics, University Erlangen Nuernberg, Erlangen, Germany
  • Friedrich E Kruse
    Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Ursula Schlötzer-Schrehardt
    Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Footnotes
    Commercial Relationships   Matthias Zenkel, None; Francesca Pasutto, None; Antonio Bergua, None; Panah Liravi, None; Steffen Uebe, None; Fulvia Ortolani, None; Friedrich Kruse, None; Ursula Schlötzer-Schrehardt, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5997. doi:
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      Matthias Zenkel, Francesca Pasutto, Antonio Bergua, Panah Liravi, Steffen Uebe, Fulvia Ortolani, Friedrich E Kruse, Ursula Schlötzer-Schrehardt; Expression of CACNA1A in Patients with Pseudoexfoliation Syndrome. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5997.

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

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Abstract

Purpose : Genetic variation in the CACNA1A gene, coding for a subunit of a Ca2+-channel, has been identified as a risk factor for pseudoexfoliation (PEX) syndrome. To determine the role of CACNA1A in the pathophysiology of PEX, we investigated its expression and localization in ocular tissues of PEX and control patients.

Methods : Twelve eyes with PEX and twelve age-matched control eyes without any known ocular disease were used. Quantitative real-time PCR analysis was applied to assess the mRNA expression of CACNA1A. Immunohistochemical analysis was performed on the light and electron microscopic level using four different antibodies against CACNA1A. Antibodies for lysyl oxidase-like 1 (LOXL1), the blood vessel markers CD31 and alpha smooth muscle actin, and the elastic fiber component fibrillin-1, were used in double labelling experiments.

Results : CACNA1A displayed a moderate mRNA expression in the trabecular meshwork, lens capsule, and retina, as well as a low expression in the cornea, iris, ciliary body and choroid. Comparing PEX and control tissues, no significant difference could be established. By immunostaining, CACNA1A was detected in virtually all ocular tissues with strong signals in vascular endothelial and vascular smooth muscle cells. Double labelling experiments confirmed a clear co-localization with blood vessel markers. A moderate staining was obtained in endothelial cells of the cornea and trabecular meshwork, both pigmented and non-pigmented ciliary epithelial cells, muscle cells of the iris and ciliary body, retinal ganglion cells, and cells of the inner and outer nuclear layer. In PEX and control eyes, CACNA1A displayed a similar protein expression and localization. Interestingly, in double labelling experiments CACNA1A staining of vascular endothelial cells was associated with LOXL1- and fibrillin-1-positive PEX deposits, particularly prominent in the iris.

Conclusions : Our data suggest that PEX-associated genetic variation in the CACNA1A gene do not affect the expression or localization of its gene product. However, the association of CACNA1A in vascular endothelial cells with PEX deposits points to an altered, PEX-specific Ca2+-homeostasis, which may lead to the stabilization of fibrillin-1, the Ca2+-dependent main component of PEX deposits. In addition, the especially prominent association of CACNA1A with PEX deposits in iridal vessel walls supports the well-documented vascular etiology of PEX syndrome.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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