Ocular toxicity of intravitreal golimumab in a rabbit model

Abstract

Background/aim: To investigate the effect of intravitreal golimumab on rabbit retina histopathology.Materials and methods: Sixteen albino New Zealand rabbits were divided into three groups. The right eye of each rabbit in groups I, II,and III received a single intravitreal injection of 5 mg/0.05 mL (6 eyes), 10 mg/0.1 mL (6 eyes), or 20 mg/0.2 mL (4 eyes) golimumab,while left eyes served as controls with the same volume of a balanced salt solution injection. All animals were examined using slit-lampbiomicroscopy and indirect ophthalmoscopy before and after intravitreal injection and at days 1 and 7. Animals were euthanized on day7 and the eyes were enucleated for immunohistochemistry evaluation and electron microscopic examination of the retinas.Results: For groups I, II, and III, the number of cells in the outer nuclear layer and the inner nuclear layer was decreased compared tothose in the control groups. In group I, the percentage of caspase-3 staining of the outer nuclear layer was significantly higher than thatin the control. For groups II and III, TUNEL and caspase-3 staining percentages in the outer and inner nuclear layers were found to besignificantly higher than those for the control groups. In the ganglion cell layer, for groups I, II, and III, neither TUNEL nor caspase-3staining percentages showed any significant difference between two groups. No significant dose-dependent relationship was found forincreasing doses of golimumab in all layers. Myelin figures and karyorrhexis in the photoreceptor cells were prominent in electronmicroscopy of the golimumab-injected eyes.Conclusion: Golimumab caused apoptosis in both photoreceptors and bipolar cells of the rabbit retina. Potential retinal toxicity ofintravitreal golimumab should be considered if an intravitreal administration is planned.