Galina Dubinsky

Development and recovery of laser-induced retinal lesion in rats.

Purpose: Laser-induced retinal lesions undergo primary and secondary degeneration followed by a partial reduction of the lesion size. To evaluate treatment effects, detailed data regarding the changes of the lesion over time are essential. The purpose of the study is to describe the histologic changes in an argon laser-induced retinal lesion over a period of 60 days. Methods: Argon laser lesions were produced in retinas of pigmented rats. The lesions were examined by light microscopy 1 hour and 1, 2, 3, 20, and 60 days after the exposure. Results: The diameter of the lesion increased 24 hours after photocoagulation and then decreased by day 20. Most pyknotic nuclei seen in the outer nuclear layer 1 hour after lasering disappeared 3 days later. Remodeling began 3 days after lasering. By day 60, partial filling in of the empty area with sliding of adjacent nuclei was observed. Recovery was also seen in the other retinal layers. Conclusion: The course of a laser-induced retinal lesion is gradual: the photoreceptors are damaged first and the damage then spreads to other layers and to the adjacent retina. By day 3, the damage spreading stops, and adjacent cells begin to fill in and remodel the area of the lesion.

Ameliorative effect of NAP on laser‐induced retinal damage

Purpose:  NAP is the smallest active element of activity‐dependent neuroprotective protein (ADNP) in the non‐myelinated neural tissue.

Intravitreal saline injection ameliorates laser-induced retinal damage in rats.

Purpose: Injury to the central nervous system has been shown to trigger a physiologic response in the form of some degree of natural self-repair. This beneficial reaction may be boosted by appropriate preconditioning via a reversible injury to the retina. Here we report the ameliorative effect of intravitreal saline injection on laser-induced retinal damage. Methods: Standard argon laser lesions (514 and 544 nm, 200 &mgr;m, 0.1 W, 0.05 seconds) were induced in the eyes of 36 Dark Agouti pigmented rats and immediately followed by injection of saline either intravitreally (5 &mgr;L) or intravenously (0.5 mL). Lesions were evaluated histologically and morphometrically after 3, 20, and 60 days. Results: At all 3 time points, the eyes of rats injected intravitreally showed less laser-induced retinal cell loss (P < 0.05) and smaller lesion diameters (P < 0.05) than those of intravenously injected rats. Conclusion: Intravitreal saline injection evidently has a neuroprotective effect on the rat retina. The mechanism of action of this effect should be further elucidated and its clinical applicability tested.

Neuroprotective vaccination with copolymer-1 decreases laser-induced retinal damage

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) in adjuvant was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions. The present study tested the neuroprotective ability of Cop-1 to reduce the spread of laser-induced retinal damage. Standard argon laser lesions were created in 72 DA pigmented rats divided into four groups: two Cop-1 treated groups (animals treated seven days before or immediately after the laser session) and two control groups treated respectively by saline or the effective but toxic neuroprotective compound MK-801. The histological and morphological evaluations of the lesions 3, 20, and 60 days after the injury revealed significant reduction in photoreceptor loss of the retinas of the pre-immunized animals. Cop-1 given after the laser injury did not prevent cell loss significantly, while the neuroprotective effect of MK-801 was observed only on the third day after the laser injury. The results show that pre-immunization with Cop-1 is neuroprotective in unmyelinated (gray matter) neural tissue such as the retina. This approach may be of clinical significance in ameliorating laser-induced retinal injuries in humans.

Development and recovery of laser-induced retinal injury in rats

Retinal photocoagulation lesions undergo primary and secondary degeneration followed by partial healing. This study follows the sequential changes in laser-induced retinal lesion over a time span of 60 days. Argon laser lesions were created in 36 pigmented rats. Sections of the retinal lesions were evaluated by light microscopy 1, 24, 48, 72 hours, and 20, and 60 days after the injury (six animals at each time point). The diameter of the lesion was equal to that of the laser spot 1h after irradiation and increased by 24h. It decreased later, slightly during the following 48h and significantly by 20 days. The destruction of photoreceptors was most severe after 24-48h. The nuclei in the outer-nuclear layer were pyknotic at the lesion site at 1h and disappeared later. Healing processes began 72h after the irradiation and was completed by 60 days. Filling-in by sliding of near nuclei was observed by the 60th day. Reversible changes were seen also in the retinal pigment epithelium (with formation of a plaque at 72h and its degradation later on) and in the choroid (disorganization of capillaries by 48h with later reorganization). Conclusions: The development of a laser-induced injury is gradual. The photoreceptors are damaged first and than the damage spreads to other layers of retina and to areas adjacent the primary injury site. The extension of the damage is later stopped and the adjacent tissues tend to fill the lesion and remodel the retina.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Copolymer-1 vaccination regimens for neuroprotection in laser-induced retinal injuries

The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1, Copaxone) in adjuvant against laser-induced retinal damage was previously reported. The present study quantitatively compares various regimens of this vaccination for reducing the spread of laser-induced retinal damage and investigates the cellular mechanism of Cop-1 activity. Standard argon laser lesions were created in 78 DA pigmented rats divided into five groups: three Cop-1 single treatment groups (treated 7 days before, immediately after, or 24 hours after the injury), one group treated twice (7 days before and 20 days after injury), and a control group treated with adjuvant 7 days before the injury. The retinal lesions were evaluated 3, 20, and 60 days after the injury. Immunostaining of the retinas of the pretreated and control group animals 3 days after the laser injury was performed for T-cell detection. Cop-1 pre-immunization reduced photoreceptor loss at all time points as measured over the central zone of the lesion and 3 and 20 days after lasing as measured over the whole damaged area. Lesion diameter was reduced only 60 days after laser injury in pre-treated animals. Cop-1 given immediately after injury reduced cell loss as measured 20 and 60 days later in the whole lesion and 20 days after the laser irradiation, when measured in the center of lesion. It had no effect on lesion diameter. Late treatment reduced only the lesion diameter at all time points. Repeated treatment enhanced the neuroprotective effect, decreasing the cell loss in the center of lesion and reducing the diameter of lesion. T-cells were detected in the retinal lesions of pre-immunized animals and not in non-treated group, demonstrating the cellular immune mechanism of Cop-1. Immunization with Cop-1 is neuroprotective against laser-induced retinal injuries, and repeating the treatment enhances this effect. Cellular immune action of Cop-1 of was detected.

The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (P<0.01). The shorter HBO treatment was less effective, showing an increase only in nuclei density at the central area of lesion (P< 0.01). Hyperbaric oxygen seems to exert a neuroprotective effect on laser-induced retinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.