ApoA-I Mimetic Peptide 4F Reduces Age-Related Lipid Deposition in Murine Bruch's Membrane and Causes Its Structural Remodeling.
Curr Eye Res
; 43(1): 135-146, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-28972410
ABSTRACT
PURPOSE:
Accumulation of lipoprotein-derived lipids including esterified and unesterified cholesterol in Bruch's membrane of human eyes is a major age-related change involved in initiating and sustaining soft drusen in age-related macular degeneration (AMD). The apolipoprotein (apo) A-I mimetic peptide 4F is a small anti-inflammatory and anti-atherogenic agent, and potent modifier of plasma membranes. We evaluated the effect of intravitreally-injected 4F on murine Bruch's membrane.METHODS:
We tested single intravitreal injections of 4F doses (0.6 µg, 1.2 µg, 2.4 µg, and placebo scrambled peptide) in ApoEnull mice ≥10 months of age. After 30 days, mice were euthanized. Eyes were processed for either direct immunofluorescence detection of esterified cholesterol (EC) in Bruch's membrane whole mounts via a perfringolysin O-based marker linked to green fluorescent protein or by transmission electron microscopic visualization of Bruch's membrane integrity. Fluorescein isothiocyanate-conjugated 4F was traced after injection.RESULTS:
All injected eyes showed a dose-dependent reduction of Bruch's membrane EC with a concomitant ultrastructural improvement compared to placebo treated eyes. At a 2.4 µg dose of 4F, EC was reduced on average by ~60% and Bruch's membrane returned to a regular pentalaminar structure and thickness. Tracer studies confirmed that injected 4F reached intraocular targets.CONCLUSION:
We demonstrated a highly effective pharmacological reduction of EC and restoration of Bruch's membrane ultrastructure. The apoA-I mimetic peptide 4F is a novel way to treat a critical AMD disease process and thus represents a new candidate for treating the underlying cause of AMD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Lâmina Basilar da Corioide
/
Lipídeos
/
Degeneração Macular
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Curr Eye Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha