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Khomthorn P. Cunvong, D. Joshua Cameron; Amyloid-β Peptide Induces Angiogenesis In The Adult Zebrafish Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6481.
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Age-related macular degeneration (AMD) is a leading cause of irreversible blindness. Amyloid-β peptide (Aβ), a hallmark of Alzheimer’s disease and found within dense aggregates and plaques in the brain, has also been found in drusen deposits in patients with AMD. Even though Aβ has been associated with these two high-profile diseases for many years, its biological function remains relatively unknown. The brain and eye possess similar neurodegenerative pathways, because they are alike in their molecular and cellular structures. Therefore, it would be correct to conclude that the eyes serve as a good indicator of brain health, and vice versa. A recent hypothesis has suggested that Aβ interacts in the Notch pathway and thereby affects angiogenesis. We are testing this hypothesis in the adult zebrafish eye.
Tg (kdr:EGPF)s843 transgenic zebrafish, expressing GFP in vascular endothelial cells, were maintained under standard conditions at 28.5°C on a 10 h dark - 14 h light cycle. Fish were sedated using Tricaine and placed under a dissecting microscope for injections, which were performed at the dorsal-most aspect of the cornea, into the aqueous humor, using pulled glass capillary needles. At 7 dpi, fish enucleated and fixed in 4% PFA at 4°C overnight. These eyes were then re-hydrated in PBS before being dissected and flat-mounted on a slide. Confocal images were taken of the retina and these images were joined together to generate a map of the retinal vessels, which include the circumferential vein.
Injection sites healed quickly, with no observable visual or physiological defects. PBS injections did not affect the blood vessel branching in the eye, whereas positive controls, injected with a γ-secretase inhibitor (GSI), showed increased vessel branching. Fish eyes that were treated with Aβ developed significantly more endothelial tip branches, as well as near the thin capillaries leading to the circumferential vein.
These findings suggest that Aβ plays a role in angiogenesis. Preliminary data suggests that Aβ specifically interacts with Notch genes, but needs further elucidation. Aβ’s role in angiogenesis could shed light on AMD and Alzheimer’s disease pathophysiology and offer new targets for therapeutic intervention.
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