BDNF Confers Long–Term Protection From the Retinal Toxicity of Verteporfin PDT

Abstract

Purpose: : We showed previously that pretreatment with BDNF reduces the retinal toxicity observed 1 week after verteporfin photodynamic therapy (PDT) in a rat model. This study examines the rescue effect of BDNF 3 months after a single course of PDT, or after two PDT treatments 3 months apart. We also test the effect of CNTF, and a combination of BDNF and CNTF.

Methods: : For PDT, adult Brown–Norway rats received 6.0 mg/m² verteporfin intravenously and 10 J/cm² laser light at 689 nm delivered to the superior retina. Some animals received a second course of PDT, 3 months after the first. Two days prior to PDT, eyes were injected intravitreally with 2 µg BDNF, 2 µg CNTF, both factors, or PBS. Retinal function was evaluated using multifocal ERG, and structure was studied using light microscopy.

Results: : Three months after a single course of PDT, BDNF–treated eyes had 30% more surviving photoreceptors than PBS–treated eyes (p<0.005). Although mfERG responses were significantly better in the BDNF–treated eyes 1 week after PDT, visual function recovered in PBS–treated eyes so that there was no difference at 3 months. Three months after a second course of PDT, 3 of 5 animals showed dramatic rescue with 60% more surviving photoreceptors (p<0.035), but 2 animals with severe damage exhibited no rescue. Pretreatment with CNTF rescued photoreceptors 1 week after PDT in most animals, but significantly depressed mfERG responses. A combination of BDNF and CNTF produced significant rescue of photoreceptors 1 week after PDT, but depressed the mfERG.

Conclusions: : Protection by BDNF from the retinal toxicity of verteporfin PDT persists 3 months after treatment and is effective through more than one course of PDT in a majority of treated animals. Adjunctive therapy with BDNF has the potential to improve long–term visual outcomes in patients treated with PDT.

Keywords: photodynamic therapy • neuroprotection • age-related macular degeneration