BASIC SCIENCE Ameliorative effect of PN-277 on laser-induced retinal damage Shiri Shulman & Mark Belokopytov & Galina Dubinsky & Michael Belkin & Mordechai Rosner Received: 14 May 2008 / Revised: 14 August 2008 / Accepted: 6 October 2008 / Published online: 6 November 2008 # Springer-Verlag 2008 Abstract Background The retinal damage induced by laser photoco- agulation increases considerably by the secondary degenera- tion process whereby tissues adjacent to the primary lesion are destroyed. As the neuroprotective effect of immunization by PN-277 was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions, it may be used also for reducing retinal damage induced by laser. The aim of this study was to evaluate the neuroprotective effect of immuni- zation with PN-277 in reducing the spread of laser-induced retinal damage. Methods Standard argon laser lesions were created in 36 DA pigmented rats. Seven days before exposure to laser, the rats were divided into a test group (n=18) that was pre- immunized with intraperitoneal injection of PN-277 and control group (n=18) treated with saline. Histological and morphometrical evaluations of the retinal lesions were preformed 3, 20, and 60 days after the injury. Results Significant ameliorative effect was demonstrated in the retinas of the pre-immunized animals 60 days after exposure to laser. The diameter of the lesion was 356 μm as compared with 406 μm (P<0.01), the cell density of the photoreceptor cell bodies measured in the whole lesion was 72.4% of normal as compared with 64.5% (P=0.01), and at the center of the lesion it was 57.3% of normal as compared with 38.2% (P<0.01) (treated and control groups, respectively). Conclusions Immunization with PN-277 has an ameliorative effect in neural tissue such as the retina. This type of immunization may be of clinical significance in reducing laser-induced retinal injuries in humans. Keywords Immunomodulation . Laser injury . Neuroprotection . Retina . Retinal injury Introduction A damage to neural cells due to any cause triggers a process of degeneration in nerve cells adjacent to the primarily injured ones [1]. This process of secondary degeneration starts by the release of various noxious compounds from the primarily injured cells that spread to the neighboring cells and damages them. This initiates a cascade of spreading damage whereby the secondarily injured neurons damage a widening area. Many compounds that are involved in the secondary degeneration were identified. These include glutamate, ionic Ca2 + , reactive oxygen species [2], nitric oxide [3] and more. The effects of these noxious agents released from the primarily injured cells result in further neuronal cell death and spread of the morphological and functional retinal damage. Many competitive and non-competitive NMDA receptor specific antagonists were tested for their ability to decrease excitotoxic damage in the retina [4]. The most effective amongst them is MK-801 [5] but neurotoxic and psycho- toxic reactions preclude its use in humans. Treatment with Graefes Arch Clin Exp Ophthalmol (2009) 247:343–348 DOI 10.1007/s00417-008-0975-4 Shiri Shulman and Mark Belokopytov contributed equally to this work. S. Shulman Ophthalmology Department, Sapir Medical Centre, Kfar –Sava, Israel M. Belokopytov : G. Dubinsky : M. Belkin : M. Rosner Goldschleger Eye Research Institute, Sackler School of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, Israel M. Belokopytov (*) Goldschleger Eye Research Institute, Sheba Medical Center, 52621 Tel Hashomer, Israel e-mail: markb120@gmail.com