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Armin Mohi, Salvatore Grisanti Grisanti, Martin Rudolf; ApoA-I Mimetic Peptide D-4F Easily Penetrates Retina and Reduces Neutral Lipids in Bruch’s Membrane Wholemounts. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5365.
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The age-related accumulation of neutral lipids in Bruch’s membrane (BrM) with concomitantly increased hydraulic resistivity is a major age change of importance to the pathogenesis of age-related macular degeneration. ApoA-I mimetic peptides are a new class of small, highly effective lipid acceptors with a high anti-inflammatory potential. In a mouse model of age-related BrM lipid deposition we evaluated the effect of the intravitreally injected peptide D-4F and we traced FITC-labeld D-4F in the period of 30 days within retina and choroid
In groups of five 8 month-old ApoEnull mice we tested 3 doses of D-4F (0.6 µg; 1.2 µg; 2.4 µg) vs sham injection. One eye per mouse received a single injection of D-4F or NaCl. The second untreated eye served as a within-individual control. Thirty days after injection eyes were enucleated and processed to BrM whole mounts. The samples were stained with a newly developed fluorescent cholesterol dye GFP-D4. The treatment effect on BrM lipid deposition was evaluated by fluorescence microscopy. Additionally 12 mice were injected 12 µg of FITC-labeled D-4F. The mice were sacrificed at different time points (1, 7, 14, 30 days). The eyes were prepared for histology and were marked with a secondary fluorescent antibody to trace intraocular D-4F
All treated eyes demonstrated a significant decrease of lipid deposition in BrM. Our preliminary data show that the fluorescence intensity was reduced in average by 32% in treated eyes in our highest dose group. FITC-D-4F could be detected in all retinal layers, BrM, and choroid as early as 1 day after injection. The fluorescence intensity within these structures increased with time. At 30 days the D-4F signal was reduced especially in the inner retina
Our data demonstrated a significant D-4F-induced reduction of BrM lipid in murine whole mount preparations after semiquantitative evaluation by fluorescence microscopy. These results are comparable to our previously tested peptide L-4F with TEM evaluation. We could also show that intravitreal injected D-4F can easily penetrate the retina and reached BrM and choroid within 24 hrs
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