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M.-M. Catrinescu, A. Kanamori, R. Beaubien, W. Chan, Z. Gross, L. A. Levin; Iron and Manganese Corroles Are Neuroprotective for Serum-Deprived Retinal Neurons. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3712.
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© ARVO (1962-2015); The Authors (2016-present)
Corroles are tetrapyrrolic macrocycles that have come under increased attention because of their unique capabilities for oxidation catalysis, reduction catalysis, and biomedical applications. Corrole-metal complexes (metallocorroles) can decompose a variety of reactive oxygen species (ROS), often more efficiently than analogous metalloporphyrins. We investigated whether bipolar Fe-, Mn- and Ga-corroles have neuroprotective effects on neurons and reduce ROS in vitro and in vivo.
Undifferentiated and differentiated RGC-5 neuronal precursor cells were induced to undergo apoptosis by serum deprivation for 48 hours. Differentiation of RGC-5 cells was induced with 316 nM staurosporine. The level of cell death with or without these metallocorroles was monitored by XTT assay and by calcein-AM/propidium iodide assay. RGC-5 ROS were measured with hydroethidine (HEt), a superoxide indicator. In vivo, real-time imaging using a confocal scanning laser ophthalmoscope (CSLO) identified the production of ROS within individual rat RGCs after optic nerve transection. Intraocular ROS was visualized by intravitreal administration of HEt.
RGC-5 cell death after serum deprivation was significantly decreased by Fe- and Mn-corroles, but not Ga-corrole. This correlated with the ability of Fe- and Mn-corroles but not Ga-corrole to dismutate intracellular superoxide, measured by fluorescence after HEt administration. In vivo, intravitreal Fe- and Mn-corroles, but not Ga-corrole decreased retinal HEt-positivity after optic nerve transection.
Fe- and Mn-corroles could be candidate drugs for delaying RGC death after axonal injury in optic neuropathies via suppression of specific ROS.
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