AAR  Vol.2 No.2 , May 2013
New antioxidant SkQ1 is an effective protector of rat neural retina under conditions of long-term organotypic cultivation
ABSTRACT

During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, “the dirtiest place in the cell” in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.


Cite this paper
Grigoryan, E. , Novikova, Y. , Kilina, O. and Philippov, P. (2013) New antioxidant SkQ1 is an effective protector of rat neural retina under conditions of long-term organotypic cultivation. Advances in Aging Research, 2, 65-71. doi: 10.4236/aar.2013.22009.
References
[1]   Chou Newell, F.W. (1992) Ophtalmology principles and concepts. 7th Edition, Mosby-Year Book, Inc., St. Louis.

[2]   Winkler, B.S., Boulton, M.E., Gottsch, J.D. and Sternberg, P. (1999) Oxidative damage and age-related macular degeneration. Molecular Vision, 5, 32-37.

[3]   Tanito, M., Nishiyama, A., Tanaka, T., et al. (2002) Change of redox status and modulation by thiol replenishment in retinal photopxidative damage. Investigative Ophthalmology and Visual Science, 43, 2392-2400.

[4]   Emirit, J., Edeas, M. and Brikaire, F. (2004) Neurogenerative diseases and oxidative stress. Biomed. Pharmacotherapy, 58, 39-46. doi:10.1016/j.biopha.2003.11.004

[5]   Roth, F., Bindewald, A., and Holz, F.G. (2004) Key-pathophysiologic pathways in age-related macular disease. Graefe’s Archive for Clinical and Experimental Ophtalmology, 242, 710-716. doi:10.1007/s00417-004-0976-x

[6]   Tezel, G. (2011) The immune response in glaucoma: A perspective on the roles of oxidative stress. Experimental Eye Research, 93,178-186. doi:10.1016/j.exer.2010.07.009

[7]   Antonenko, Y.N., Avetisyan, A.V., Bakeeva, L.E., et al. (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: Synthesis and in vitro studies. Biochemistry, 73, 1273-1287. doi:10.1134/S0006297908120018

[8]   Lieberman, E.A., Topali, V.P., Tsofina, L.M., et al. (1969) Mechanism of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature, 222, 1076-1078. doi:10.1038/2221076a0

[9]   Bakeeva, L.E., Barskov, I.V., Egorov, M.V., et al. (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS-and age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke). Biochemistry, 73, 1288-1299. doi:10.1134/S000629790812002X

[10]   Agapova, L.S., Chernyak, B.V., Domnina, L.V., et al. (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 3. Inhibitory effect of SkQ1 on tumor development from p53-deficient cells. Biochemistry, 73, 1300-1316. doi:10.1134/S0006297908120031

[11]   Neroev, V.V., Archipova, M.M., Bakeeva, L.E., et al. (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals. Biochemistry, 73, 1317-1328.

[12]   Skulachev, V.P. (2005) How to clean the dirtiest place in the cell: Cationic antioxidants as intramitochondrial ROS scavengers. Life, 57, 305-310.

[13]   Grigoryan, E.N., Novikova, Y.P., Gancharova, O.S., et al. (2012) New antioxidant SkQ1 is an effective protector of rat eye retinal pigment epithelium and choroids under conditions of long-term organotypic cultivation. Advances in Aging Research, 4, 31-37. doi:10.4236/aar.2012.12004

[14]   Grigoryan, E.N., Novikova, Y.P., Kilina, O.V. and Philippov, P.P. (2007) New method of in vitro culturing of pigment retinal epithelium in the structure of the posterior eye sector of adult rat. Bulletin of Experimental Biology and Medicine, 4, 618-625. doi:10.1007/s10517-007-0389-z

[15]   Dizhur, A.M., Nekrasova, E.R. and Filippov, P.P. (1991) New 26 kDa protein specific for photoreceptor cells, capable of binding with immobilized delipidized rhodopsin. Biokhimiiya, 56, 225-229.

[16]   Osborne, N.N. (2008) Pathogenesis of ganglion “cell death” in glaucoma and neuroprotection: Focus on ganglion cell axonal mitochondria. Progress in Brain Research, 173, 339-352. doi:10.1016/S0079-6123(08)01124-2

 
 
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