Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate.
OBJECTIVE
To examine the effect of indomethacin, a cyclooxygenase (CO) inhibitor, on laser-induced subretinal neovascularization (SRN) in the monkey. The CO pathway of arachidonic acid metabolism plays an important role in angiogenesis, and the inhibition of CO is known to inhibit angiogenesis in the cornea and in certain tumors.


METHODS
A cannula was implanted into the vitreous cavity of 11 eyes of six monkeys and connected to an osmotic minipump. Indomethacin (25 micrograms/d) was delivered into the vitreous through the cannula for 14 days (seven eyes). Vehicle alone was injected for 14 days as a control (four eyes). Argon laser photocoagulation was then performed (eight spots at the posterior pole in each eye) to induce SRN. Fundus photographs and fluorescein angiograms were taken periodically to document the evolution of SRN. Light and electron microscopic examination was performed on two eyes of each group 8 weeks after photocoagulation.


RESULTS
Subretinal neovascularization developed from 2 to 4 weeks after photocoagulation. The incidence of SRN, indicated by fluorescein leakage, was significantly lower (P < .05) in the group treated with indomethacin (14.3%, eight of 56 lesions) than in the control group (37.5%, 12 of 32 lesions). After 8 weeks, no fluorescein leakage was found in either the control or indomethacin-treated groups. Scar formation was found on histologic examination in both groups. No histologic evidence of indomethacin toxicity was seen in the adjacent retina.


CONCLUSIONS
Intravitreal administration of indomethacin inhibits the formation of laser-induced SRN in monkey eyes. This is consistent with the participation of the CO pathway in the process of SRN formation and suggests that this pathway could be a potential target in the treatment of SRN.
Sakamoto
T
T
Doheny Eye Institute, University of Southern California, School of Medicine, Los Angeles.
Soriano
D
D
Nassaralla
J
J
Murphy
T L
TL
Oganesian
A
A
Spee
C
C
Hinton
D R
DR
Ryan
S J
SJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002404:Catheterization; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007213:Indomethacin / Q000008:administration & dosage* / Q000494:pharmacology; D015918:Infusion Pumps, Implantable; D053685:Laser Therapy; D008252:Macaca fascicularis; D012160:Retina / Q000187:drug effects* / Q000601:surgery / Q000648:ultrastructure; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014822:Vitreous Body
D007213:Indomethacin