An experimental study to evaluate safety/toxicity of intravitreal natalizumab
2018
Purpose: The purpose of this prospective experimental study was to evaluate the safety/toxicity of α4β1 integrin blockade in rabbit retina using its monoclonal antibody (
Natalizumab). Methods: Twelve New Zealand albino rabbits were divided into three groups ( n = 4). Unilateral intravitreal injections of three different concentrations of
natalizumabwere performed in every rabbit of each group (Group A: 0.625 mg, Group B: 1.25 mg, and Group C: 2.5 mg). Baseline electroretinogram (
ERG) and
fundus photographywere performed prior to injection. At days 1, 7, and 21 postinjection,
ERGand
fundus photographyof each eye were performed. At last follow-up, Group C animals with highest drug concentration were sacrificed and the enucleated eyes were evaluated for retinal toxicity using transmission electron microscopy (TEM). Results: No difference in
ERGresponses was observed in eyes injected with low and intermediate concentration of
natalizumabbetween day 0 and day 21. Furthermore, rabbits injected intravitreally with highest dose showed reduction in amplitude of “a” wave ( P = 0.0017) and a reduction in amplitude of “b” wave of
ERGat day 21 ( P = 0.0117). TEM revealed changes in the
outer plexiform layerand
inner nuclear layer, suggestive of toxicity primarily to the photoreceptor
synaptic terminalsand bipolar cells. Conclusion: Low-dose (0.625 mg) and intermediate-dose (1.25 mg) intravitreal injection of
natalizumabappears safe for rabbit retina. However, functional and anatomical changes were observed in rabbit retina following a high-dose (2.5 mg) intravitreal injection of a monoclonal antibody blocking α4β1 integrin.
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