April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Enhanced Detection Of The Anti-Aging Protein α-Klotho In Several Rodent Models Of Retinitis Pigmentosa
Author Affiliations & Notes
  • Pietro Farinelli
    Ophthalmology, Clinical Sciences, Lund, University of Lund, Lund, Sweden
    Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany
  • Blanca Arango-Gonzalez
    Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany
  • Jasvir Kaur
    Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany
  • Eberhart Zrenner
    Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany
  • François Paquet-Durand
    Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany
  • Per A. Ekström
    Ophthalmology, Clinical Sciences, Lund, University of Lund, Lund, Sweden
  • Footnotes
    Commercial Relationships  Pietro Farinelli, None; Blanca Arango-Gonzalez, None; Jasvir Kaur, None; Eberhart Zrenner, None; François Paquet-Durand, None; Per A. Ekström, None
  • Footnotes
    Support  Swedish Research Council Medicine; KMA; Torsten och Ragnar Söderbergs Stiftelser; Kerstan Foundation; Stiftelsen f. synskadade i f.d. Malmöhus län
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1814. doi:
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      Pietro Farinelli, Blanca Arango-Gonzalez, Jasvir Kaur, Eberhart Zrenner, François Paquet-Durand, Per A. Ekström; Enhanced Detection Of The Anti-Aging Protein α-Klotho In Several Rodent Models Of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1814.

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

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Abstract

Purpose: : The various forms of retinitis pigmentosa involve hereditary degeneration of photoreceptors, which may be seen as a premature aging of these cells. The α-klotho gene, encoding a type-I membrane protein that is related to β-glucuronidases, has been shown to be linked to aging in mammals, such that it appears to confer anti-aging properties. Furthermore, klotho deficient mice display aging related phenotypes. Our aim was to find out whether the klotho protein is connected to the photoreceptor degeneration in retinitis pigmentosa and therefore several rodent models of this disease were compared.

Methods: : Retinae were collected from mice of either wild type, rd1 or rd2 origin. In addition, retinae were taken from wild type rats and P23H-1 and S334ter-3 rhodopsin mutants. Postnatal ages were selected so as to reflect time points with extensive photoreceptor degeneration. The collected specimens were fixed, cryo-sectioned and immunolabeled for klotho proteins using several relevant antibodies. Klotho staining was in some cases performed in combination with TUNEL staining. Western blot of selected retinal samples was also performed.

Results: : Staining for α-klotho in any layer was only very rarely seen in the retinas from wild type mice and rats. This was in clear contrast to specimens from the above named rodent mutants, which presented α-klotho with clear and distinct staining in a subpopulation of their photoreceptors. The immunopositive cells appeared in a fashion that corresponded to numbers and localization of degenerating photoreceptors in all of the mutants. When combined with TUNEL staining it was furthermore possible to show how klotho positivity overlapped with cell death. Western blot indicated reaction with retinal proteins of molecular weights that could relate to both full length and modified protein.

Conclusions: : The presence of klotho immunoreactivity was detected in photoreceptors undergoing degeneration in all of the models. The frequency and localization of the positive cells, together with cases of co-staining for TUNEL, points to a relation to the degeneration process. Such a relation could concern increased expression due to a cellular attempt of increasing the life-span of the affected cells, although a direct involvement in the degenerative cell death machinery per se cannot be excluded.

Keywords: retinal degenerations: cell biology • photoreceptors • apoptosis/cell death 
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