Wirkung verschiedener Therapeutika in einer durch Hypoxie oder oxidativen Stress geschädigten Organkultur der Schweineretina

"Effect of different therapeutics in an organ culture of porcine rentina damaged by hypoxia or oxidative stress"

Hypoxia and oxidative stress are pathomechanisms that are involved in several retinal diseases, such as glaucoma. Hypoxia can be chemically induced by cobalt chloride (CoCl2), whereas hydrogen peroxide (H2O2) can cause oxidative stress.
Based on two established models of cultured porcine retinae (Hurst 2017; Kuehn 2017), the potential neuroprotective effect of the iNOS-inhibitor was tested in this dissertation.
In another study the neuroprotection by the antioxidant coenzyme q10 (CoQ10) was examined.
The effect of the iNOS-inhibitor was investigated using both models, in which either hypoxic processes were mimicked by CoCl2 (300 µM), or triggered by oxidative stress induced by 300 µM H2O2. The effect of CoQ10 was only examined in the model of oxidative stress. The treatment with 500 µM of the iNOS-inhibitor 1400W lasted 72 h, that with CoQ10 48 h.
Retinal ganglion cells were immunohistochemically labeled with anti-RBPMS antibody, then counted using ImageJ and finally analyzed post hoc using a one-factorial ANOVA followed by a Tuckey test.
The use of the iNOS-inhibitor in the hypoxia model was able to produce a significant protection of the retinal ganglion cells after four and eight days. CoCl2 resulted in a significant loss of retinal ganglion cells at four and eight days in comparison to the control retinas.
In a second project, the retinal ganglion cells were significantly protected from oxidative stress by the iNOS-inhibitor. H2O2 resulted in a significant loss of retinal ganglion cells after four and eight days of cultivation, whereas the iNOS-inhibitor protected the retinal ganglion cells from oxidative stress after four and eight days.
In comparison, the use of 100 and 300 µM CoQ10 did not lead to any significant protection of the retinal ganglion cells.
Hypoxia and oxidative stress induced by CoCl2 and H2O2 result in a significant loss of retinal ganglion cells. Both degeneration models serve as suitable models to investigate potential neuroprotective agents. As shown in the iNOS-inhibitor studies, the iNOS-inhibitor 1400W protects the retinal ganglion cells against both pathomechanisms.
For further studies, more retinal cells should be investigated to get a better understanding of the exact mechanism of the iNOS-inhibitor.
CoQ10 as a possible neuroprotectant should also be further explored.