June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Testing a new pharmacological therapy approach for the removal of lipofuscin in vitro: results from a newly established culture of aged primary Stargardt mouse model RPE cells and aged primary human RPE cells
Author Affiliations & Notes
  • Tatjana Taubitz
    Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tuebingen, Germany
  • Yuan Fang
    Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tuebingen, Germany
  • Monika Rittgarn
    Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tuebingen, Germany
  • Ulrich Schraermeyer
    Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tuebingen, Germany
    STZ OcuTox Preclinical Drug Assessment, Hechingen, Germany
  • Sylvie Julien-Schraermeyer
    Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tuebingen, Germany
  • Footnotes
    Commercial Relationships   Tatjana Taubitz, None; Yuan Fang, None; Monika Rittgarn, None; Ulrich Schraermeyer, Katairo (P); Sylvie Julien-Schraermeyer, Katairo (P)
  • Footnotes
    Support  BMBF Funding: Removage - 01GQ1422B
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 257. doi:
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      Tatjana Taubitz, Yuan Fang, Monika Rittgarn, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer; Testing a new pharmacological therapy approach for the removal of lipofuscin in vitro: results from a newly established culture of aged primary Stargardt mouse model RPE cells and aged primary human RPE cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):257.

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

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Abstract

Purpose : Stargardt disease and dry age-related macular degeneration (AMD) are two lipofuscin-related diseases for which currently no treatment exists. A number of therapeutic approaches that try to limit the formation of lipofuscin are under investigation. We previously described the tetrahydropyridoether class of compounds that can remove existing lipofuscin from retinal pigment epithelium (RPE) cells in vivo (Julien & Schraermeyer, 2012. doi:10.1016/j.neurobiolaging.2011.12.009).
Here, we present in vitro results from the tetrahydropyridoether compound Remofuscin® that shows no cytotoxicity in aged Stargardt mouse RPE cells and shows a phenotypical and functional rescue in aged primary human RPE cells.

Methods : A model of aged primary mouse RPE cell culture (pigmented Abca4-/- mice, 12 months and older) was established. Cells were treated with Remofuscin® and tested for cytotoxic effects (Life/Dead assay, TUNEL assay) and proliferation (Ki67 staining). Also, aged primary human RPE cells (donors aged 59 – 84 years) were treated with Remofuscin® and fed with porcine rod outer segments (ROS). Imaging flow cytometry (ImageStream®X Mark II) was used to quantify lipofuscin autofluorescence, as well as phagocytosis activity and digestion of ROS.

Results : After treatment with Remofuscin®, primary mouse RPE cells showed a significant reduction of dead cells and TUNEL positive cells compared to untreated controls. Proliferation was not influenced by the treatment. Preliminary data of primary human RPE cells suggest a considerable loss of lipofuscin autofluorescence and an elevation of phagocytosis after treatment compared to untreated controls.

Conclusions : Current results indicate that Remofuscin® treatment has no cytotoxic effects in vitro, and induces removal of lipofuscin and an increase of ROS phagocytosis. These data point to Remofuscin® being a promising drug for to-date untreatable lipofuscin-related diseases like Stargardt disease and dry AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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