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Superoxide Dismutase 1 Nanozyme for Treatment of Eye Inflammation.

Abstract
Use of antioxidants to mitigate oxidative stress during ocular inflammatory diseases has shown therapeutic potential. This work examines a nanoscale therapeutic modality for the eye on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1), termed "nanozyme." The nanozyme is produced by electrostatic coupling of the SOD1 with a cationic block copolymer, poly(L-lysine)-poly(ethyleneglycol), followed by covalent cross-linking of the complexes with 3,3'-dithiobis(sulfosuccinimidylpropionate) sodium salt. The ability of SOD1 nanozyme as well as the native SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with immunogenic uveitis. Results suggested that topical instillations of both enzyme forms demonstrated anti-inflammatory activity; however, the nanozyme was much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as the intensities of corneal and iris edema, hyperemia of conjunctiva, lens opacity, fibrin clots, and the protein content in aqueous humor. Clinical findings were confirmed by histological data. Thus, SOD1-containing nanozyme is potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.
AuthorsOlga A Kost, Olga V Beznos, Nina G Davydova, Devika S Manickam, Irina I Nikolskaya, Anna E Guller, Petr V Binevski, Natalia B Chesnokova, Anatoly B Shekhter, Natalia L Klyachko, Alexander V Kabanov
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2015 Pg. 5194239 ( 2015) ISSN: 1942-0994 [Electronic] United States
PMID26697135 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Polymers
  • Recombinant Proteins
  • Succinimides
  • 3,3'-dithiobis(sulfosuccinimidyl propionate)
  • Superoxide Dismutase
  • Superoxide Dismutase-1
Topics
  • Animals
  • Conjunctiva (metabolism, pathology)
  • Polymers (chemistry)
  • Rabbits
  • Recombinant Proteins (biosynthesis, chemistry, therapeutic use)
  • Succinimides (chemistry)
  • Superoxide Dismutase (chemistry, genetics, therapeutic use)
  • Superoxide Dismutase-1
  • Uveitis (drug therapy, metabolism, pathology)

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