The effect of anakinra on retinal function in isolated perfused vertebrate retina.

PURPOSE: Blockage of the interleukin 1 (IL-1) signaling pathway has been proposed for treatment of inflammatory disorders like those affecting the retina and its adjacent tissue. Herein, we evaluated one of those inhibitory drugs, anakinra (Kineret®), based on its safety profile with emphasis on retinal function from an electrophysiological point of view. METHODS: Bovine retina preparations were perfused with two different concentrations of anakinra (1 mg/ml and 2 mg/ml). An electroretinogram (ERG) was recorded and b-wave recovery assessed. RESULTS: Exposure to anakinra at a concentration of 1 mg/ml did not decrease the b-wave amplitude, whereas 2 mg/ml resulted in a significant reduction. CONCLUSIONS: Based on these preliminary results, anakinra at a dose as low as 1 mg/ml could be regarded as safe for retinal function. However, dosages of 2 mg/ml and more do have toxic electrophysiological effects, at least for the short-term.

The effect of disease-modifying antirheumatic drugs on retinal function in the electrophysiological ex vivo model of the isolated perfused vertebrate retina.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) have been suggested in the treatment of inflammatory ophthalmological diseases. The aim of the present study was to investigate the effects of these DMARDs on bovine retinal function. METHODS: Bovine retina preparations were perfused with a standard solution. After recording stable electroretinograms the nutrient solution was substituted by a DMARD medium with varying concentrations of different drugs (etanercept and infliximab) for 30 min. Afterwards b-wave recovery was observed. RESULTS: Significant decreases in the b-wave amplitude (p < 0.05) were found for etanercept 0.5 mg/ml (p = 0.0022). Infliximab 2 mg/ml (p = 0.1276) did not result in any statistically significant b-wave reduction. CONCLUSION: The presented data suggest that infliximab might have the better safety profile than etanercept.

The isolated perfused bovine retina--a sensitive tool for pharmacological research on retinal function.

The electroretinogram (ERG) of the isolated bovine retina serves as a proven criterion of retinal activity. It is used as a sensitive pharmacological tool for testing effects of applied drugs and toxins on photoreceptors, and higher order neurons that contribute to the generation of the b-wave. Following isolation and detachment from the underlying pigment epithelium, part of the retina was mounted into a closed chamber and perfused by a nutrient solution. Flow rate of the nutrient solution and its ingredients, incubation temperature and light intensity were optimised empirically to achieve a maximum b-wave amplitude. Under these conditions, a reproducible, high-resolution ERG can be stably recorded for more than 10 h with sufficient oxygenation found to be a prerequisite for the long-lasting stability. Addition of L(+)glutamate to the nutrient solutions was not anymore beneficial for the b-wave amplitude. A well-known inhibitor of oxidative phosphorylation (KCN) and antagonists of voltage-gated Ca2+ channels (isradipine, omega-conotoxin-GVIA and NiCl2) were used to prove the validity of the test system. The recording of the ERG from the isolated and perfused bovine retina serves as a valuable physiological model for a neuronal network in which important questions related to the retinal signalling and metabolism can be investigated.