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D Joshua Cameron, Eric A Saidi, Pinakin Gunvant Davey; The effect of A2E and zeaxanthin on visual function: Modelling AMD pathogenesis and treatment in zebrafish.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5127.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration is a devastating eye disorder that is characterized by the progressive loss of macular or central vision as patients age. One aspect of AMD’s pathogenesis involves the bisretinoid A2E, which accumulates with age and has been found in greater abundance in AMD eyes. Despite years of study, A2E is still somewhat of an enigma. Carotenoids have been used to delay the progression of AMD, but most studies have focused on combinations of carotenoids rather than individual compounds. We set out to test two hypotheses: 1) intracameral injections of A2E will negatively affect visual function in zebrafish. 2) Injection of zeaxanthin into the zebrafish eye would improve/protect the visual acuity of the zebrafish.
Visual acuity, calculated in cycles per degree, was measured in adult zebrafish to establish a consistent baseline using the optokinetic response. Either Zeaxanthin or A2E were dissolved into phosphate buffered saline (PBS) and injected into the anterior chamber of the right and left eyes. PBS was injected as a control into the anterior chamber of the right and left eyes of a separate group of fish. Visual acuities were measured at 1 week and 3, 8 and 12 weeks post-injection to compare to baseline values. A paired t-test was used to compare visual acuities between subjects injected with zeaxanthin or A2E and PBS.
Intraocular injections of 50µM A2E impair visual function in adult zebrafish. 2 weeks after injection visual acuity is significantly reduced (p=0.01 n= 9 for each group). Zeaxanthin injections on the other hand showed a significant improvement in visual acuity, 22% better than before the injection (p=0.02 n=11 for zexanthin and 10 for PBS). This improvement peaked at more than 30% for some fish a few weeks after the injection. The enhanced visual function returned to normal 3 months after the initial injection.
A2E caused a significant reduction in visual function while zeaxanthin actually improved visual function in the adult zebrafish. Further studies looking at the histology and other aspects of visual function will help in characterizing the mechanism behind these observed visual acuity changes and aid in understanding the pathogenesis of AMD. Additionally, this platform may serve as a model for studying the etiology of AMD and possible treatments.
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