Research Paper Volume 12, Issue 7 pp 6151—6171

Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease

Figure 6. Effect of norbixin late curative supplementation from 12 to 17 months in Abca4-/- Rdh8-/- mice. (A) Schematic representation of the 5-month late curative supplementation protocol design. (B) Scotopic A wave ERG recorded after 5 months of oral supplementation with norbixin in Abca4-/- Rdh8-/- mice compared to mice fed with normal chow (vehicle) and to 1.5- and 12-month-old mice. (C) Scotopic B wave. (D) Photopic B wave. (E) Quantification of photoreceptor nuclear layers along the superior and inferior poles of the retina each measured every 200 μm apart from the optic nerve. (F) A2E quantification in eyes from 12-month-old Abca4-/- Rdh8-/- mice, 17-month-old mice fed with normal chow or with norbixin-containing pellets. (G) Representative images of lipofuscin content in RPE cells of 17-month-old vehicle and norbixin-treated mice. Large granules of lipofuscin are found in the RPE cytoplasm (white asterisk). (H) Histograms showing the quantified lipofuscin granules expressed by area of 100 μm2. (I) Histograms representing the surface of cytoplasm occupied by lipofuscin and expressed in percentage of total cytoplasm surface. Bars represent mean ± s.e.m. with n = 8 per group (i.e. n=16 eyes per group for ERG). *p<0.05, **p<0.01 compared to vehicle (One-way ANOVA, Dunnett's post-test).