July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Loss of Translocator Protein 18 kDa (TSPO) in the retinal pigment epithelium (RPE) of mice may lead to impaired visual function and abnormal RPE morphology
Author Affiliations & Notes
  • Katrin Klee
    Lab for Retinal Cell Biology , University of Zurich, Schlieren, Switzerland
  • Federica Storti
    Lab for Retinal Cell Biology , University of Zurich, Schlieren, Switzerland
  • Joshua L Dunaief
    Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Thomas Langmann
    Experimental Immunology of the Eye, University of Cologne, Cologne, Germany
  • Christian Grimm
    Lab for Retinal Cell Biology , University of Zurich, Schlieren, Switzerland
  • Footnotes
    Commercial Relationships   Katrin Klee, None; Federica Storti, F.Hoffmann-La Roche Ltd, Basel, Swtizerland (F); Joshua Dunaief, None; Thomas Langmann, None; Christian Grimm, None
  • Footnotes
    Support  VELUX Stiftung
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2460. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Katrin Klee, Federica Storti, Joshua L Dunaief, Thomas Langmann, Christian Grimm; Loss of Translocator Protein 18 kDa (TSPO) in the retinal pigment epithelium (RPE) of mice may lead to impaired visual function and abnormal RPE morphology. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2460. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : TSPO is upregulated in microglia, astrocytes and to some extent in neurons of damaged areas in the pathologic brain. Modulation of TSPO with specific ligands yields positive outcomes in paradigms of brain diseases and retinal degeneration. This beneficial effect of TSPO ligands is mainly attributed to the dampening of microglia activation. Recently, however, we found that TSPO is strongly and constitutively expressed also in the RPE. Here we address the role of TSPO in the mouse RPE for retinal homeostasis.

Methods : RPE-specific knock-out of Tspo was achieved by breeding BEST1-Cre with Tspoflox/flox mice. Specificity of CRE activity was tested in reporter mice. Tspoflox/flox;BEST1-Cre (RPEΔTspo), littermates Tspoflox/flox (RPECtrl) and BEST1-Cre mice were followed up for up to 6-months of age by fundus imaging, optical coherence tomography (OCT) and electroretinography (ERG). Morphology was analyzed by light microscopy on semi-thin plastic sections. Tspo knock-out was tested by immunofluorescence (IF). Gene expression was determined by real-time PCR.

Results : IF showed that TSPO was strongly expressed in the RPE of adult wild type mice. Tspo mRNA was detected in the RPE and neural retina as early as at post-natal day 1. Expression in the RPE increased during post-natal development. BEST1-Cre activity was restricted to the RPE but patchy, resulting in a mixed population of RPE cells that were or were not depleted of TSPO in RPEΔTspo mice. Fundus appearance and retinal layering were not affected but ERG recordings revealed a trend toward reduced b-wave amplitudes in RPEΔTspo mice. Although RPEΔTspo mice had a normal retinal morphology they developed droplet-like structures in the RPE. The number of affected cells and droplets per cells increased from 2- to 6-months of age.

Conclusions : Lack of TSPO in the mouse RPE might have an impact on retinal function without grossly affecting retinal morphology or fundus appearance. The development of droplet-like inclusions in the RPE of RPEΔTspo mice suggests an involvement of TSPO in RPE metabolism. Further characterization of the droplets may help to unveil the function of TSPO in the RPE and determine how it might influence retinal function.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×