Abstract
Simulation of hypoxic processes in vitro can be achieved through cobalt chloride (CoCl2), which induces strong neurodegeneration. Hypoxia plays an important role in the progression of several retinal diseases. Thus, we investigated whether hypoxia can be reduced by hypothermia. Porcine retinal explants were cultivated for four and eight days and hypoxia was mimicked by adding 300 µM CoCl2 from day one to day three. Hypothermia treatment (30 °C) was applied simultaneously. Retinal ganglion, bipolar and amacrine cells, as well as microglia were evaluated via immunohistological and western blot analysis. Furthermore, quantitative real-time PCR was performed to analyze cellular stress and apoptosis. In addition, the expression of specific marker for the previously described cell types were investigated. A reduction of ROS and stress markers HSP70, iNOS, HIF-1α was achieved via hypothermia. In accordance, an inhibition of apoptotic proteins (caspase 3, caspase 8) and the cell cycle arrest gene p21 was found in hypothermia treated retinae. Furthermore, neurons of the inner retina were protected by hypothermia. In this study, we demonstrate that hypothermia lowers hypoxic processes and cellular stress. Additionally, hypothermia inhibits apoptosis and protects neurons. Hence, this seems to be a promising treatment for retinal neurodegeneration.
Highlights
A deprived oxygen supply in tissues is known as hypoxia and can occur in several retinal diseases, such as glaucoma[1]
We evaluated the effects of different CoCl2 concentrations on porcine retinae and demonstrated that it induced neuronal cell loss, which was associated with increased apoptosis mechanisms[11]
PH-measurements were performed after each medium exchange, and reactive oxygen species (ROS) level was evaluated on days one and two
Summary
A deprived oxygen supply in tissues is known as hypoxia and can occur in several retinal diseases, such as glaucoma[1]. Divalent metal ions, such as cobalt, can cause oxidative stress by rupturing the outer cell membrane and disturbing the mitochondrial respiration. These mechanisms of cellular toxicity have been proposed for several neurodegenerative disorders. We evaluated the effects of different CoCl2 concentrations on porcine retinae and demonstrated that it induced neuronal cell loss, which was associated with increased apoptosis mechanisms[11]. The goal of our study was to investigate possible neuroprotective effects of hypothermia in a CoCl2 induced degeneration model of cultured porcine retinal explants. Bipolar and amacrine cells as well as glial cells were assessed after four and eight days of cultivation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
