Chronic N–4–Hydroxyphenyl Retinamide Treatment Augments Laser Induced Choroidal Neovascularization in Mice

Abstract

Purpose: : N–4–hydroxyphenyl retinamide (4–HPR; fenretinide) is a retinoic acid derivative and a stimulator of endogenous ceramide biosynthesis that has been shown to be cytotoxic to tumor cells. Generation of reactive oxygen species is one mechanism by which 4–HPR causes cytotoxicity. The purpose of the study was to assess the effect of chronic administration of 4–HPR on laser induced choroidal neovascularization (CNV) in mice.

Methods: : Focal laser photocoagulation (Diode green laser, 75–µm spot size, 0.1–second duration, 140 mW) was applied to eyes of adult, male C57BL/6 mice. Three laser photocoagulation burns were delivered to the retina, lateral to the optic disc through a slit lamp using a coverglass as a contact lens. 4–HPR (1mg, 0.4ml) or vehicle was injected intraperitoneally 2x daily for 14 days after laser photocoagulation. Fluorescein angiograms (FA) and histological examinations were performed at day 7 and day 14 after laser surgery.

Results: : Administration of 4–HPR resulted in increased levels of vascular leakage shown by FA. Histological studies revealed increased CNV lesion size in mice treated with 4–HPR compared to controls. In addition, there were fewer retinal pigmented epithelial cells in the CNV lesions of mice treated with 4–HPR compared to controls.

Conclusions: : 4–HPR treatment resulted in increased CNV as compared to controls, possibly due to increased oxidative stress. The exact mechanism of action of 4–HPR remains to be elucidated.

Keywords: choroid: neovascularization • oxidation/oxidative or free radical damage • age-related macular degeneration