Sakamoto T, Soriano D, Nassaralla J, Murphy T L, Oganesian A, Spee C, Hinton D R, Ryan S J
Doheny Eye Institute, University of Southern California, School of Medicine, Los Angeles.
Arch Ophthalmol. 1995 Feb;113(2):222-6. doi: 10.1001/archopht.1995.01100020106040.
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.
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.
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.
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.
研究环氧化酶（CO）抑制剂吲哚美辛对猴激光诱导性视网膜下新生血管形成（SRN）的影响。花生四烯酸代谢的CO途径在血管生成中起重要作用，已知抑制CO可抑制角膜和某些肿瘤中的血管生成。
将一根套管植入6只猴11只眼的玻璃体腔，并与一个渗透微型泵相连。通过套管将吲哚美辛（25微克/天）注入玻璃体，持续14天（7只眼）。单独注射赋形剂14天作为对照（4只眼）。然后进行氩激光光凝（每只眼后极部8个光斑）以诱导SRN。定期拍摄眼底照片和荧光素血管造影照片，记录SRN的演变过程。光凝8周后，对每组的2只眼进行光镜和电镜检查。
光凝后2至4周出现视网膜下新生血管。吲哚美辛治疗组（14.3%，56个病变中有8个）荧光素渗漏显示的SRN发生率显著低于对照组（37.5%，32个病变中有12个）（P <.05）。8周后，对照组和吲哚美辛治疗组均未发现荧光素渗漏。两组组织学检查均发现瘢痕形成。在相邻视网膜中未发现吲哚美辛毒性的组织学证据。
玻璃体腔内注射吲哚美辛可抑制猴眼激光诱导性SRN的形成。这与CO途径参与SRN形成过程一致，并提示该途径可能是治疗SRN的潜在靶点。
