Nanoparticles C60 fullerene prevent reactive gliosis in retina of aged rats under hyperglycemia
AbstractReactivation of glial cells, induced by metabolic disorders of glucose utilization and development of oxidative stress in retina under diabetes mellitus, is the key pathogenetic factor of diabetic retinopathy. Nanoparticles of C60 fullerene and some of their water-soluble derivates are known as one of the strongest antioxidants having neuroprotective effect in a number of pathologies and harmful influences. In the present study, for the first time, the effects of nanostructures of hydrated C60 fullerene (C60HyFn) on the expression and polypeptide composition of glial fibrillary acidic protein (GFAP) in retina of rats with streptozotocin (STZ)-induced diabetes have been evaluated. Using immunoblotting, 1.93-fold up-regulation of GFAP in diabetic rat retina as compared with control was shown, as a result of retinal glial cells reactivation induced by hyperglycemia. Increase in GFAP-immunolabeling associated with the reactive gliosis development in retina of diabetic rats was also confirmed by immuno-histochemical method. Consumption of C60HyFn solution (90 nM) as drinking water by diabetic rats for 12 weeks caused 1.51-fold decrease of GFAP level compared to untreated diabetic animals. In addition, C60HyFn caused statistically significant lowering of glycosylated hemoglobin concentration in blood serum of STZ-diabetic rats 1.58-fold. However, nanoparticles C60 did not affect neither insulin nor glucose levels in blood of diabetic rats. In conclusion, results obtained indicate that protective action of hydrated fullerene in the initial period of diabetic retinopathy of aged animals is realized through suppression of excessive activation of GFAP-positive retinal cells.
Andrievsky, G., Bruskov, V.I., Tykhomyrov, A.A., Gudkov, S.V., 2009. Peculiarities of the antioxidant and radioprotective effects of hydrated C60 fullerene nanostuctures in vitro and in vivo. Free Rad. Biol. Med. 47, 786–793. >>doi: 10.1016/j.freeradbiomed.2009.06.016
Bradford, M.M., 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254. >> doi: 10.1016/0003-2697(76)90527-3
Dringen, R., Pawlowski, P.G., Hirrlinger, J., 2005. Peroxide Detoxification by brain cells. J. Neurosci. Res. 79, 157–165. >> doi: 10.1002/jnr.20280
Etem, E.O., Bal, R., Akağaç, A.E., Kuloglu, T., Tuzcu, M., Andrievsky, G.V., Buran, I., Nedzvetsky, V.S., Baydas, G., 2014. The effects of hydrated C(60) fullerene on gene expression profile of TRPM2 and TRPM7 in hyperhomocysteinemic mice. J. Recept. Signal. Transduct. Res. 34(4), 317–324. >> doi: 10.3109/10799893.2014.896381
Ganesh, B.S., Chintala, S.K., 2011. Inhibition of reactive gliosis attenuates excitotoxicity-mediated death of retinal ganglion cells. PLoS ONE 6, e18305. >> doi: 10.1371/journal.pone.0018305
Haurigot, V., Villacampa, P., Ribera, A., Llombart, C., Bosch, A., Nacher, V., Ramos, D., Ayuso, E., Segovia, J.C., Bueren, J.A., Ruberte, J., Bosch, F., 2009. Increased intraocular insulin-like growth factor-I triggers blood-retinal barrier breakdown. J. Biol. Chem. 284(34), 22961–22969. >> doi: 10.1074/jbc.M109.014787
Jiang, T., Chang, Q., Zhao, Z., Yan, S., Wang, L., Cai, J., Xu, G., 2012. Melatonin-mediated cytoprotection against hyperglycemic injury in Müller cells. PLoS One 7(12), e50661. >> doi: 10.1371/journal.pone.0050661
Klein, B.E., Knudtson, M.D., Tsai, M.Y., Klein, R., 2009. The relation of markers of inflammation and endothelial dysfunction to the prevalence and progression of diabetic retinopathy: Wisconsin epidemiologic study of diabetic retinopathy. Arch. Ophthalmol. 127(9), 1175–1182. >> doi: 10.1001/archophthalmol.2009.172
Liu, B., Ma, X., Guo, D., Guo, Y., Chen, N., Bi, H., 2012. Neuroprotective effect of alpha-lipoic acid on hydrostatic pressure-induced damage of retinal ganglion cells in vitro. Neurosci. Lett. 526(1), 24–28. >> doi: 10.1016/j.neulet.2012.08.016
Mamczur, P., Borsuk, B., Paszko, J., Sas, Z., Mozrzymas, J., Wiśniewski, J.R., Gizak, A., Rakus, D., 2015. Astrocyte-neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes. Glia 63(2), 328–330. >> doi: 10.1002/glia.22753
Nedzvetsky, V., Andrievsky, G., Chachibaia, T., Tykhomyrov, A., 2012. Differences in antioxidant/protective efficacy of hydrated C60 fullerene nanostructures in liver and brain of rats with streptozotocin-induced diabetes. J. Diabetes Metab. 3(8), 1–9. >> doi: 10.4172/2155-6156.1000215
Pellerin, L., Magistretti, P.J., 2012. Sweet sixteen for ANLS. J. Cereb. Blood Flow Metab. 32, 1152–1166. >> doi: 10.1038/jcbfm.2011.149
Rungger-Brandle, E., Dosso, A.A., Leuenberger, P.M., 2000. Glial reactivity, an early feature of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 41(7), 1971–1980.
Sugaya-Fukasawa, M., Watanabe, T., Tamura, M., Egashira, S., Hisatomi, H., 2010. Glial fibrillary acidic protein is one of the key factors underlying neuron-like elongation in PC12 cells. Exp. Ther. Med. 2(1), 85–87.
Tan, S.M., Deliyanti, D., Figgett, W.A., Talia, D.M., de Haan, J.B., Wilkinson-Berka, J.L., 2015. Ebselen by modulating oxidative stress improves hypoxia-induced macroglial Müller cell and vascular injury in the retina. Exp. Eye Res. 136, 1–8.
Tarr, J.M., Kaul, K., Chopra, M., Kohner, E.M., Chibber, R., 2013. Pathophysiology of diabetic retinopathy. Hindawi Publish. Corp. ISRN Ophthalmol. ID 343560, 1–13. >> doi: 10.1155/2013/343560
Tykhomyrov, A.A., Nedzvetsky, V.S., Klochkov, V.K., Andrievsky, G.V., 2008. Nanostructures of hydrated C60 fullerene (C60HyFn) protect rat brain against alcohol impact and attenuate behavioral impairments of alcoholized animals. Toxicology 246(2–3), 158–165. >> doi: 10.1016/j.tox.2008.01.005
Ulas, M., Orhan, C., Tuzcu, M., Ozercan, I.H., Sahin, N., Gencoglu, H., Komorowski, J.R., Sahin, K., 2015. Anti-diabetic potential of chromium histidinate in diabetic retinopathy rats. BMC Complement. Altern. Med. 15(16), 1–8.
Zong, H., Ward, M., Stitt, A.W., 2011. AGEs, RAGE, and diabetic retinopathy. Diabet. Rep. 11(4), 244–252. >> doi: 10.1007/s11892-011-0198-7
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.