Date: 20 Dec 2009

The safety profile of alkylphosphocholines in the model of the isolated perfused vertebrate retina

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Abstract

Background

Alkylphosphocholines (APCs) are synthetic phospholipid derivatives, and have been demonstrated to inhibit ocular cell proliferation in vitro and in vivo. Currently, they are applied clinically for their antitumoral and antiparasitic properties, but have not yet been implemented for clinical use in proliferative ophthalmic disorders. The purpose of this study was to assess the safety of APC in the ex vivo model of the isolated perfused vertebrate retina.

Methods

Bovine retina preparations were perfused with an oxygen pre-equilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl-electrodes. After recording stable b-wave amplitudes, an APC was applied at the following concentrations to the nutrient solution: 0.25 µM, 2.5 µM and 25 µM. To investigate the effects of APC on photoreceptor function, a test series at the same concentrations was performed to evaluate the effects of APC on the a-wave amplitude. Aspartate at a concentration of 1 mM was added to the nutrient solution to obtain stable a-wave amplitudes. Thereafter, APC was applied at the same concentrations to the nutrient solution. The recovery of the ERG amplitudes was followed up for 75 minutes.

Results

No reduction of the a- and b-wave amplitude was found at the end of the exposure time with APC added in each test series. No differences were found between the ERG amplitudes before and after application of APC at the end of the washout.

Conclusions

In the ex vivo model of the isolated perfused vertebrate retina, APC has proved to be a safe compound in the concentrations applied. Thus, APCs should further be considered as promising candidates for future clinical applications in ophthalmology.

Matthias Lüke and Kai Januschowski contributed equally.