Since 1995, 11 million animals per year were used for research purposes in the EU, an average of 2.5 million in Germany alone, with an upward trend. 1 Ophthalmological research also frequently uses laboratory animals. An important field of research is the understanding of retinal degeneration, as its causes are not yet fully understood preventing successful treatment.In the last years, we developed retinal organ culture models, to test new therapies without euthanasia of laboratory animals. [2][3][4][5] These models are based on porcine retinae, which can be obtained as a waste product from the food industry. The morphology and
AbstractNitrite oxide plays an important role in the pathogenesis of various retinal diseases, especially when hypoxic processes are involved. This degeneration can be simulated by incubating porcine retinal explants with CoCl 2 . Here, the therapeutic potential of iNOS-inhibitor 1400W was evaluated. Degeneration through CoCl 2 and treatment with the 1400W were applied simultaneously to porcine retinae explants.Three groups were compared: control, CoCl 2 , and CoCl 2 + iNOS-inhibitor (1400W).At days 4 and 8, retinal ganglion cells (RGCs), bipolar, and amacrine cells were analysed. Furthermore, the influence on the glia cells and different stress markers were evaluated. Treatment with CoCl 2 resulted in a significant loss of RGCs already after 4 days, which was counteracted by the iNOS-inhibitor. Expression of HIF-1α and its downstream targets confirmed the effective treatment with 1400W. After 8 days, the CoCl 2 group displayed a significant loss in amacrine cells and also a drastic reduction in bipolar cells was observed, which was prevented by 1400W. The decrease in microglia could not be prevented by the inhibitor. CoCl 2 induces strong degeneration in porcine retinae by mimicking hypoxia, damaging certain retinal cell types.Treatment with the iNOS-inhibitor counteracted these effects to some extent, by preventing loss of retinal ganglion and bipolar cells. Hence, this inhibitor seems to be a very promising treatment for retinal diseases. K E Y W O R D S hypoxia, iNOS-inhibitor 1400W, organ culture, retina, retinal ganglion cells | 4313 HURST eT al. How to cite this article: Hurst J, Mueller-Buehl AM, Hofmann L, et al. iNOS-inhibitor driven neuroprotection in a porcine retina organ culture model. J Cell Mol Med. 2020;24:4312-4323. https://doi.