Optimization of Copolymer–1 Vaccination regimen for Neuroprotection in Laser–Induced Retinal Injuries

Abstract

Abstract: : The retinal damage induced by laser photocoagulation increases manifold by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. The neuroprotective effect of immunization by glatiramer acetate (Copolymer–1, Cop–1) on the retina against laser–induced damage was previously reported (Belokopytov M, et al. IOVS 2003;44:ARVO E–Abstract 5247). Purpose: This study quantitatively compared the neuroprotective ability of various regimens of vaccination by Cop–1 in order to reduce the spread of laser–induced retinal damage. Methods: Standard argon laser lesions were created in 78 DA pigmented rats divided into five groups (six animals for each time point in each group): three Cop–1 single treatment groups (animals treated 7 days before, immediately after, or 24 hours after the laser injury), one group treated twice (7 days before and 20 days after the laser irradiation), and a control group treated with Complete Freund’s Adjuvant 7 days before the injury. Results: The histological and morphological evaluation of the lesions 3, 20, and 60 days after the injury revealed significant reduction in photoreceptor loss in the pre–immunized animals at all time points as measured over the central zone of the lesion. The same protective effect was observed 3 and 20 days after lasing as measured over the whole damaged area. Significant reduction in lesion diameter after pretreatment with Cop–1 was seen only 60 days after laser injury. Cop–1 given immediately after the laser damage reduced cell loss 20 and 60 days after the laser damage, when measured in the whole lesion and 20 days after the laser irradiation, when measured in the center of lesion. The immediate treatment had no effect on lesion diameter. Treatment by Cop–1 24 hours after the laser session had no effect on cell density, but reduced the lesion diameter at all time points. Repeating the treatment once, 20 days after the injury, led to enhancement of the neuroprotective effect, decreasing the cell loss in the center of lesion and reducing the diameter of lesion. Conclusions: The results show that immunization with Cop–1 is neuroprotective against laser–induced retinal injuries, and repeating the treatment enhances this effect.

Keywords: neuroprotection • immunomodulation/immunoregulation • laser