gms | German Medical Science

26. Jahrestagung der Deutschen Retinologischen Gesellschaft

Deutsche Gesellschaft für Retinologie

27.09.2013, Hamburg

Apolipoprotein mimetic Dual Domain Peptide reduces Neutral Lipid Deposits in murine Bruch's Membrane

Meeting Abstract

  • Armin Mir Mohi Sefat - Lübeck, Germany
  • S. Grisanti - Lübeck, Germany
  • C. Örün - Lübeck, Germany
  • M. Rudolf - Lübeck, Germany

Retinologische Gesellschaft. 26. Jahrestagung der Retinologischen Gesellschaft. Hamburg, 27.-27.09.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. Doc13rg09

doi: 10.3205/13rg09, urn:nbn:de:0183-13rg097

Veröffentlicht: 20. August 2013

© 2013 Mir Mohi Sefat et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Purpose: Massive accumulation of neutral lipids in Bruch’s membrane (BrM) with concomitantly increased hydraulic resistivity and oxidative stress induction is a major age change in the eye and an important pathogenic factor for the development and progression of age-related macular degeneration. Apolipoprotein (Apo) mimetic peptides are highly effective and well tolerated lipid acceptors that might be used to remove these pathogenic deposits. We evaluated the effect of an intravitreally injected dual domain peptide (DDP) containing domain properties of ApoE and ApoA1 in an established mouse model of age-related BrM lipid deposition (ApoEnull).

Methods: Four groups (4x; n=6) of 10 month-old ApoEnull mice received a single intravitreal injection of DDP with different dosages (0 µg; 0.6 µg; 1.2 µg; 2.4 µg). The second untreated eye served as an intraindividual control. Thirty days after injection all animals were sacrificed and eyes were enucleated and processed to BrM wholemounts. The specimens were stained with a protocol for BrM specific esterified cholesterol using the fluorescent cholesterol specific dye PFO/D4-GFP (Dettbarn et al. ARVO 2010). The treatment effect on BrM lipid deposition was evaluated semiquantitatively by fluorescence measurements. We calculated for each dose group across all treated vs. untreated eyes the relative difference (%) and tested for significance using the student-t-test.

Results: The vehicle injection (0.9% NaCl, 0 µg DDP) caused no change in BrM esterified cholesterol content (p=0.29). In all other groups we could observe a significant decrease of cholesterol content depending on the DDP dose administered. The lowest dose showed a mild but significant effect (p<0.001) of –16.2% cholesterol reduction in the treated eyes vs. untreated eyes. The medium and highest DDP dose showed also significant effects (p<0.001) with a cholesterol reduction of –41.7% in the medium dose group and –34.2% with the highest dose.

Conclusions: Our data demonstrated a significant and dose dependant reduction of BrM lipid deposits by DDP with ApoA1- and ApoE domain characteristics. Nevertheless, the treatment effect is lower than with our initially tested ApoA1 mimetic peptides (L-4F, D-4F, ARVO 2011 Rudolf et al. Mohi et al.). A neutral lipid reduction of ca. 70% with a single intravitreal injection of 2.4 µg D-4F shows almost double the treatment effect of the here tested DDP.