Format

Send to

Choose Destination
Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):461-472. doi: 10.1167/iovs.18-25786.

Apolipoprotein A-I Mimetic Peptide L-4F Removes Bruch's Membrane Lipids in Aged Nonhuman Primates.

Author information

1
Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
2
Translational AMD Research Group Lübeck, University of Lübeck, Lübeck, Germany.
3
Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States.
4
Department of Ophthalmology, University of Erlangen, Erlangen, Germany.
5
Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
6
German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Germany.
7
University Heart Centre Lübeck, Lübeck, Germany.
8
Laboratory for Angiogenesis & Ocular Cell Transplantation, University of Lübeck, Lübeck, Germany.
9
Institute of Biomedical Optics, University of Lübeck, Lübeck, Germany.

Erratum in

  • Erratum [Invest Ophthalmol Vis Sci. 2019]

Abstract

Purpose:

Multiple evidence lines support Bruch's membrane lipid deposition as a major precursor of soft drusen and age-related macular degeneration as including a potentially treatable atherosclerosis-like progression in the subretinal pigment epithelium (RPE)-basal lamina space. We evaluated the effect of anti-inflammatory, antiatherogenic peptide L-4F on Bruch's membrane of aged nonhuman primates in a dose-escalating study.

Methods:

Macaca fascicularis ≥20 years of age evaluated by color fundus photography and optical coherence tomography received monocular intravitreal injections of L-4F (n = 7) or a placebo-scrambled peptide (n = 2) in 6 doses of 25 to 175 μg over 6 months. Eyes were processed for detection and masked semiquantitative assessment of macular Bruch's membrane neutral lipid (oil red O staining), esterified cholesterol (filipin histochemistry), membrane attack complex (immunofluorescence), and paramacular thickness (transmission electron microscopy).

Results:

Bruch's membrane neutral lipid, esterified cholesterol, and membrane attack complex were cleared and ultrastructure was improved in L-4F-injected eyes, compared to placebo-injected eyes. Fellow eyes were also affected to the same degree as the injected eyes. Punctate yellow fundus lesions without corresponding RPE elevations on optical coherence tomography correlated to RPE lipoidal degeneration (engorgement with lipid droplets), which was unchanged by this treatment.

Conclusions:

Clinical-stage apolipoprotein A-I mimetic peptide L-4F, delivered intravitreally in repeated doses, produced a substantial pharmacologic reduction of Bruch's membrane lipid and restoration of ultrastructure in a nonhuman primate model that exhibits an important precursor of soft drusen, if not soft drusen themselves.

PMID:
30707219
DOI:
10.1167/iovs.18-25786
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center