Protective effect of the extremolytes ectoine and hydroxyectoine in a porcine organ culture
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Protective effect of the extremolytes ectoine and hydroxyectoine in a porcine organ culture Teresa Tsai 1 & Ana M. Mueller-Buehl 1 & Yathavan Satgunarajah 1 & Sandra Kuehn 1 & H. Burkhard Dick 1 & Stephanie C. Joachim 1 Received: 11 December 2019 / Revised: 17 June 2020 / Accepted: 15 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Hypoxic damage to the retina is a relevant component of neurodegenerative pathologies such as glaucoma or retinal ischemia. In porcine retina organ cultures, hypoxic damage can be induced by applying cobalt chloride (CoCl2). The aim of our study was to investigate possible neuroprotective effects of the extremolytes ectoine and hydroxyectoine in this hypoxiadamaged retina model. Methods To simulate hypoxia, porcine retina organ cultures were damaged with 300 μM CoCl2 for 48 h starting on day 1 (n = 8– 9/group). In order to investigate the possible neuroprotective effects of ectoine and hydroxyectoine, 0.5 mM of each extremolyte was added to the culture at the same time as the stressor and for the same duration. On day 8, the retina organ cultures were taken for (immuno)-histochemical examinations. Retinal ganglion cells (RGCs), macroglia, and apoptotic and hypoxic cells were detected with appropriate markers followed by cell counts and group comparisons. Results Treatment with ectoine resulted in RGC protection (p < 0.05) and reduced rate of apoptosis (p < 0.001) in hypoxiatreated retina organ cultures. However, the macroglia area and the amount of hypoxic, HIF-1α+ cells were unaffected by the ectoine treatment (p = 0.99). Treatment with hydroxyectoine also protected RGCs (p < 0.01) by inhibiting apoptosis (p < 0.001). In addition, the number of hypoxic, HIF-1α+ cells could be significantly reduced by treatment with hydroxyectoine (p < 0.05). The macroglia area on the other hand was unchanged after CoCl2 and treatment with hydroxyectoine. Conclusion Both extremolytes had a protective effect on CoCl2-induced hypoxia in the porcine retina organ culture. Regarding the reduction of hypoxic stress, hydroxyectoine appears to be more effective. Thus, both extremolytes represent an interesting potential new therapeutic approach for patients with ocular diseases in which hypoxic processes play a significant role. Keywords Extremolytes . Ectoine . Hydroxyectoine . Hypoxia . Porcine organ culture
Introduction Hypoxia refers to a mismatch between oxygen demand and oxygen supply, so that a condition exists in which the tissue is not sufficiently supplied with oxygen. Both the structural and functional integrity of the retina depend on its oxygenation. As one of the most metabolically active tissues, oxygen is Teresa Tsai and Ana M. Mueller-Buehl contributed equally to the work presented here and should therefore be regarded as equivalent authors. * Stephanie C. Joachim [email protected] 1
Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany
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