Small molecule screen for compounds that affect vascular  development in the zebrafish retina.
Blood vessel formation in the vertebrate eye is a precisely regulated process. In the human retina, both an excess and a deficiency of blood vessels may lead to a loss of vision. To gain insight into the molecular basis of vessel formation in the vertebrate retina and to develop pharmacological means of manipulating this process in a living organism, we further characterized the embryonic zebrafish eye vasculature, and performed a small molecule screen for compounds that affect blood vessel morphogenesis. The screening of approximately 2000 compounds revealed four small molecules that at specific concentrations affect retinal vessel morphology but do not produce obvious changes in trunk vessels, or in the neuronal architecture of the retina. Of these, two induce a pronounced widening of vessel diameter without a substantial loss of vessel number, one compound produces a loss of retinal blood vessels accompanied by a mild increase of their diameter, and finally one other generates a severe loss of retinal vessels. This work demonstrates the utility of zebrafish as a screening tool for small molecules that affect eye vasculature and presents several compounds of potential therapeutic importance.
Kitambi
Satish S
SS
School of Life Sciences, Södertörns University College, Sweden.
McCulloch
Kyle J
KJ
Peterson
Randall T
RT
Malicki
Jarema J
JJ
D015766:Albendazole / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D008463:Mebendazole / Q000737:chemistry / Q000494:pharmacology; D010641:Phenotype; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects* / Q000196:embryology*; D054852:Small Molecule Libraries / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology*
D054852:Small Molecule Libraries; D008463:Mebendazole; D015766:Albendazole