Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization.
Ocular neovascular diseases represent a major cause of blindness in the world. Angiostatic steroids are a unique class of compounds which inhibit the formation of new blood vessels in various models, including ocular models of angiogenesis. In search of potent new anti-angiogenic agents for the treatment of ocular neovascular disease, a large group of steroids were evaluated for angiostatic activity in the chick embryo CAM model. Angiostatic activity was found among all steroid classes included in the study. There was a good correlation between the angiostatic efficacies of 15 diverse steroids tested in the chick CAM and in the rabbit LPS-induced corneal pocket models of neovascularization (r=0.76, p=0.01). These studies show that potent angiostatic steroids inhibit neovascularization in two different animal models, suggesting a common mechanism of action. Glucocorticoid therapy is sometimes associated with ocular side effects. Two of the most potent angiostatic steroids, AL-3789 and AL-4940, were evaluated for glucocorticoid-mediated antiinflammatory activity in the in vitro U937 cell model of LPS-induced IL-1 induction and found to be devoid of glucocorticoid activity. Angiostatic steroids which lack glucocorticoid activity should be attractive drug candidates for treating ocular neovascular disease.
McNatt
L G
LG
Alcon Laboratories, Inc., Fort Worth, Texas 76134, USA.
Weimer
L
L
Yanni
J
J
Clark
A F
AF
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002642:Chick Embryo; D002829:Choroid / Q000098:blood supply*; D020256:Choroidal Neovascularization / Q000517:prevention & control*; D003315:Cornea / Q000098:blood supply* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011817:Rabbits; D013256:Steroids / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects
C108423:AL 3789; D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D013256:Steroids; C108424:Anecortave; D006854:Hydrocortisone