Retinal toxicity to triamcinolone acetonide's vehicle: an electrophysiology and electron microscopy study

To assess rabbit retinal toxicity to triamcinolone acetonide vehicle, benzyl alcohol, when injected intravitreally. This prospective comparative experimental study included 24 pigmented rabbits assigned into 2 groups; group 1 [experiment, n=12] received intravitreal 0.1ml of benzyl alcohol [BA], and group 2 [control, n=12] received intravitreal 0.1ml of balanced salt solution [BSS]; all injections were done in the right eyes. Clinical examinations were done on both eyes of all available rabbits before injection, at 1 and 3 hours post injection, and together with electroretinograms [ERGs] at 3, 7, 14, 28 and 42 days following injections. Three rabbits from each group were killed at 7, 14, 28 and 42 days and both eyes were sent for either light or electron microscopic examination for quantitative morphometric measurements. Mean amplitudes of ERG a and b waves of the BA-injected eyes were 6.42 +/- 9.02 micro v and 11.18 +/- 15.18 micro v at 3 days respectively, which was significantly reduced compared to the BSS-injected eyes [30.87 +/- 8.22 micro v and 57.90 +/- 13.38 micro v, respectively; p<0.01 t-test] and the non-injected contralateral eyes [36.20 +/- 7.85 micro v and 64.10 +/- 9.36 micro v, respectively; p<0.01 t-test]. These ERG responses continued to be significantly reduced in the BA-injected eyes [p<0.01 t-test] of the unkilled rabbits up to 6 weeks. The mean ganglion cell count [at a magnification of X200 in a standard frame of 4740.32 micro m[2]] were significantly reduced [p<0.005 t-test] in the BA-injected eyes [8.42 +/- 2.4] compared to the BSS- and non-injected eyes [16.42 +/- 3.9 and 16.5 +/- 4.2, respectively]. The mean inner nuclear layer [INL] and outer nuclear layer [ONL] thickness were significantly reduced [p<0.005 t-test] in the BA-injected eyes [3.78 +/- 0.96 micro m and 11.77 +/- 1.29 micro m, respectively] compared to the BSS- [6.1 +/- 0.92 micro m and 21.82 +/- 0.95 micro m, respectively] and non-injected eyes [7.05 +/- 1.9 micro m and 22.49 +/- 1.0/micro m, respectively]. Electron microscopy showed intracellular irreversible changes in the GCL, INL, ONL, and PRL at 6 weeks in group 1, with no significant changes in group 2. There was no significant rise in the intraocular pressure or clinical evidence of increased lens density during the study period. Triamcinolone Acetonide's Vehicle, benzyl alcohol, produced severe irreversible ERG and structural damage to rabbit neurosensory retinal following intravitreal injection

Methanol induced retinal and hepatic toxicity in the rat model and role of antioxidants

Human methanol poisoning is characterized by serious visual impairment, hepatic toxicity and formic acidemia. Non-primate species are resistant to the accumulation of formate and the associated methanol toxicity. A non-primate model of methanol induced toxicity was developed using adult albino rats treated with subanaesthetic concentrations of nitrous oxide to inhibit the oxidation of methanol's toxic metabolites. Methanol intoxicated rats developed retinal and hcpatic toxicity as well as metabolic acidosis analogous to methanol toxicity in humans. This work was conducted on 140 adult albino rats divided into 5 groups. The first group [control group] was further subdivided into 6 subgroups each consisted of 10 rats. The other 4 groups consisted of 20 rats each. Group Ia was the negative control group, group lb received 2 mL normal saline orally, group Ic was exposed to a mixture of N20: 02 [1:1 flow rate 3 liters/min] for 4 hours, group Id was given methyl alcohol orally in a dose of 4 g/kg followed by further 2 doses [2 g/kg] at 12 and 24 hours after the initial dose, group Ie was given N-acetyl cysteine orally in a dose of 100 mg/kg 30 mill and repeated every 8 hours for further 3 doses, and group If was given melatonin orally in a dose of 30 mg/kg 30 min and repeated every 8 hours for further 3 doses. Group II was exposed to N20: 02 mixture for 4 hours followed by methanol administration orally in a dose of 4 g/kg followed by further 2 doses [2 g/kg] at 12 and 24 hours after the initial dose. Group III was exposed to the mixture of N20: 02 for 4 hours then was given methyl alcohol as in group II then N-acetyl cysteine as mentioned before. Group IV was exposed to the mixture of N20: 02 for 4 hours then was given methyl alcohol as in group 11 then melatonin as mentioned before. Group V was exposed to the mixture of N20: O2 for 4 hours then was given methyl alcohol as in group 11 then N-acetyl cysteine and melatonin together in the same doses and timing as groups III and IV. At the end of the experimental period, the animals were anaesthetized for fundus examination. Then the animals were sacrificed, blood samples were withdrawn for measuring arterial blood gases and malondialdehyde [MDA], the eyeballs and livers were taken for histopathological study. The biochemical results revealed highly significant changes in pH, bicarbonate and malondialdehye concentrations in methanol intoxicated rats [group II]. On administration of N-acetyl cysteine or melatonin after methanol intoxication, there was significant decrease in lipid peroxidation products [MDA] especially with melatonin but the pH changes were not improved. As regard to ocular examination there was a significant improvement in optic disc and retinal edema especially when melatonin and N-acetyl cysteine were given together. Histopathological results of the liver and retina revealed an improvement with either N-acetyl cysteine or melatonin, however, melatonin was more protective. The combination of both antioxidants gave the best results. From the results of this study, It can be concluded that melatonin and/or N-acetyl cysteine have protective effects against methanol-induced ocular and hepatic toxicity