Inhibition of Experimental Choroidal Neovascularization by Irsogladine, an Anti-Gastric Ulcer Agent

Abstract

Purpose: To determine whether irsogladine inhibits experimental choroidal neovascularization (CNV) induced by laser photocoagulation in pigmented rats. Methods: Focal laser photocoagulation (argon green 50 mW, 0.04 s, 200 µm) was applied to the retinochoroid of normal Brown Norway rats. Oral administration of irsogladine (5 mg/kg/day or 50 mg/kg/day) was started 1 week before and continued for 2 weeks after laser photocoagulation. Choroidal vascular casts were made 2 weeks after laser photocoagulation and were examined with a scanning electron microscope (SEM). CNV formation was classified according to three grades and evaluated. Results: Laser-induced CNV formation was significantly reduced in rats given 5 mg/kg/day (p < 0.01) or 50 mg/kg/day of irsogladine (p < 0.001). Administration of 50 mg/kg/day of irsogladine was more effective in preventing CNV formation than 5 mg/kg/day (p < 0.001). The development of the vascular bud was especially inhibited by 50 mg/kg/day of irsogladine (p < 0.001). CNVs in rats treated with 50 mg/kg/day of irsogladine looked less well developed than those in controls. There was no significant side effect of irsogladine. Conclusions: Irsogladine inhibits the development of experimental CNV induced by photocoagulation in pigmented rats.

Evaluation of Retinal Pigment Epithelium and Choroidal Neovascularization in Rats Using Laser-Scanning Optical-Resolution Photoacoustic Microscopy

“…We speculated that the black antenna-like structure originated from CNV and extended above RPE, and the shadow can be seen easily because of the bright background caused by RPE high-amplitude PA signals. It has been shown that capillary buds initiate the formation and development of CNV [51]. The number of "capillary buds" is closely related to CNV activity.…”

Suppression of Laser-Induced Choroidal Neovascularization by Subconjunctival Injection of 9.ALPHA.-Fluoromedroxyprogesterone Acetate (FMPA), an Anti-angiogenic Agent, in Rats

“…Recently, several anti-angiogenic agents, including TNP-470, irsogladine and anecortave acetate, have been investigated to verify their potential for clinical use as a new drug for CNV. 9,11,14,[24][25][26] FMPA is a synthetic analog of MPA. It has been widely used as a therapeutic agent for breast and endometrium cancers without unacceptable side effects, and synthesized in order to enhance its anti-tumor and anti-angiogenic activities by fluorinating MPA.…”

“…The laser-induced CNV model in rats has been widely used for study of CNV. [10][11][12][24][25][26][27] The essential process of CNV formation in this model, including the break-up of the basement membrane, the migration and proliferation of vascular endothelial cells and the tubular formation, is similar to the naturally-occurring process. In this study, FMPA inhibited the incidence of CNV formation by subconjunctival injection, and it was thus thought that FMPA might be useful drug for treating CNV.…”

“…Therefore drug therapy for CNV with minimal damage to the healthy retina is under investigation and many anti-angiogenic agents have been evaluated. [9][10][11][12][13][14][15][16] Angiogenesis is an important process by which new blood vessels are formed from preexisting microvessels in many diseases such as cancer, diabetic retinopathy, and exudative AMD. 17) It has been reported that anecortave acetate, an angiostatic steroid, is clinically efficacious for improving vision in patients with exudative AMD.…”