Open AccessiNOS‐inhibitor driven neuroprotection in a porcine retina organ culture model
Author(s) -
Hurst José,
MuellerBuehl Ana Maria,
Hofmann Lisa,
Kuehn Sandra,
Herms Fenja,
Schnichels Sven,
Joachim Stephanie Christine
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15091
Subject(s) - neuroprotection , retinal , retina , hypoxia (environmental) , microglia , explant culture , chemistry , nitric oxide synthase , retinal degeneration , pharmacology , microbiology and biotechnology , pathology , biology , nitric oxide , medicine , immunology , neuroscience , biochemistry , endocrinology , inflammation , in vitro , organic chemistry , oxygen
Nitrite 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.