Retinal Damage Caused by Photodynamic Therapy Can Be Reduced Using BDNF

Abstract

Age related macular degeneration (AMD) is the leading cause of blindness among the elderly in the United States (Klein et al., 1992; Klein et al., 2002), and choroidal neovascularization (CNV) accounts for the majority of severe vision loss (Ferris et al., 1984). The current standard treatment for CNV is verteporfin photodynamic therapy (PDT) (Landy and Brown, 2003), which uses a laser to activate a photosensitizing dye accumulated within the CNV. Although PDT causes less damage to the retina overlying CNV than thermal laser, in normal primate (Husain et al., 1996; Kramer et al., 1996; Reinke et al., 1999; Peyman et al., 2000), rabbit (Peyman et al., 2000) and rat (Zacks et al., 2002) models, PDT damages photoreceptors and retinal pigment epithelial (RPE) cells. Although there has been no histologic evidence of damage to normal human retinal cells after PDT (Schlotzer-Schrehardt et al., 2002), patients treated with PDT experience visual disturbances and acute severe vision loss significantly more often than patients receiving placebo (Arnold et al., 2004; Azab et al., 2004). Because neurotrophic agents, such as brain-derived neurotrophic factor (BDNF) have been proven effective in reducing retinal damage in rodents after exposure to constant light (LaVail et al., 1992; Okoye et al., 2003), we hypothesized that BDNF treatment prior to PDT might reduce collateral damage to retinal and RPE cells in normal rats.