Methylene blue prevents neurodegeneration caused by rotenone in the retina
- 260 Downloads
An experimental optic neuropathy model was used to test the hypothesis that methylene blue may protect the retinal ganglion cell layer from neurodegeneration caused by rotenone. Rotenone is a widely used pesticide that inhibits complex I, the first enzyme of the mitochondrial respiratory chain. Complex I dysfunction is linked to the degeneration of retinal ganglion cells in Leber’s optic neuropathy. Methylene blue is a reduction-oxidation agent that can act as a powerful antioxidant and also as an enhancer of the electron transport chain, preventing formation of mitochondrial oxygen free radicals and promoting oxygen consumption. The neurodegeneration of the retina was studied in mice with intravitreal microinjection of rotenone alone, or in combination with increasing doses of methylene blue, in one eye, and the vehicle in the contralateral control eye. The effect of rotenone and rotenone plus methylene blue was investigated using two histological stains, complex I and Nissl, and two measurements, morphometric layer thickness and non-biased stereological cell counts. Rotenone induced neurodegeneration in the retinal ganglion cell layer 24 h after injection, as indicated by significant reductions in both the thickness and cell numbers of the retinal ganglion cell layer of eyes microinjected with rotenone as compared to the control eyes. This neurodegeneration was prevented in a dose dependent manner by the injection of methylene blue along with rotenone. It was concluded that rotenone-induced degeneration in the ganglion cell layer can be prevented by intravitreal injection of methylene blue.In vitro experiments showed that methylene blue is both a powerful antioxidant as well as an enhancer of cellular oxygen consumption and is able to reverse the oxidative stress and decrease in oxygen consumption induced by rotenone in brain homogenates. The findings suggest that methylene blue may be a promising neuroprotective agent in optic neuropathy and perhaps other neurodegenerative diseases caused by mitochondrial dysfunction.
KeywordsMethylene blue Rotenone Neurodegeneration Neuroprotection Optic neuropathy
Unable to display preview. Download preview PDF.
- Drager UC and JF Olsen (1981) Ganglion cell distribution in the retina of the mouse. Invest.Ophthalmol. Vis. Sci. 20, 285–293.Google Scholar
- Gonzalez-Lima F and A Cada (1998) Quantitative histochemistry of cytochrome oxidase activity, In:Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease (Gonzalez-Lima F, Ed.) (Plenum Press: New York, NY), 55–90.Google Scholar
- Gonzalez-Lima F, J Valla and L Jorandby (1998) Cytochrome oxidase inhibition in Alzheimer’s disease, In:Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease (Gonzalez-Lima F, Ed.) (Plenum Press: New York, NY), 171–200.Google Scholar
- Martinez JL Jr, RA Jensen, BJ Vasquez, T McGuinness and JL McGaugh (1978) Methylene blue alters retention of inhibitory avoidance responses.Physiol. Psychol.6, 387–390.Google Scholar
- United States National Toxicology Program (1990) Chemical Status Report. NTP Chemtrack System.Google Scholar
- Valla J, K Chen, JD Berndt, F Gonzalez-Lima, SR Cherry, D Games and EM Reiman (2002) Effects of image resolution on autoradiographic measurements of posterior cingulate activity in PDAPP mice: implications for functional nrain imaging studies of transgenic mouse models of Alzheimer’s disease.NeuroImage 16, 1–6.PubMedCrossRefGoogle Scholar