title: Amyloid-β increases capillary bed density in the adult zebrafish retina.
abstract: OBJECTIVE
  Amyloid-beta (Aβ) is an endogenous peptide that becomes dysregulated in AMD and Alzheimer disease. Both of these disorders are marked by extracellular deposits that contain Aβ, highly branched capillary networks, and neurodegeneration. Although Aβ has been implicated in AMD and Alzheimer pathology for decades, its nonpathological function has remained unclear. We recently showed that high levels of monomeric Aβ induce blood vessel branching in embryonic zebrafish brain, and here we report that a similar mechanism may contribute to aberrant blood vessel branching in the retina of adult zebrafish.
  
  
  METHODS
  Transgenic zebrafish expressing enhanced green fluorescence protein (EGFP) in their endothelial cells were sedated and small intraocular injections of PBS were made into one eye and either Aβ or γ-secretase inhibitor were injected into their opposite eye. A week later, the eyes were enucleated and high resolution maps of the retina vasculature were created using confocal microscopy. Comparisons were made between the treatment groups using the general linear model ANOVA.
  
  
  RESULTS
  We found that Aβ significantly affects capillary blood vessels in the retina. Small volumes of Aβ injected into the eyes of adult zebrafish induced the formation of significantly more endothelial tip cells and capillary bridges-some with loops-near the circumferential vein. These effects were dose-dependent and increased capillary bed density, though there was no effect on larger arterial vessels.
  
  
  CONCLUSIONS
  This study reveals a previously unknown role for Aβ in regulating capillary bed density, providing new insight into the normal biological function. Aβ will help in the development of therapeutic interventions for AMD and Alzheimer disease.
authors: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California, USA.
authors: Khomthorn
authors: K
authors: Cunvong
authors: Daniel
authors: D
authors: Huffmire
authors: Douglas W
authors: DW
authors: Ethell
authors: D Joshua
authors: DJ
authors: Cameron
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D002196:Capillaries / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D056965:Injections, Intraocular; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000139:chemically induced* / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D016229:Amyloid beta-Peptides; D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D053829:Amyloid Precursor Protein Secretases