ИСТИНА

Inflammatory diseases, including ocular ones, are accompanied by excessive production of reactive oxygen species (ROS) and by depletion of endogenous antioxidants. Even a minor damage caused by the ROS activation in the eye can affect its functions resulting in a loss of optical transparency of cornea and lens as well as disorders of hydrodynamics and the functioning of photoreceptor apparatus. The free radical processes enhancement was shown to occur in the course of development of almost all types of ophthalmic pathology (inflammations, eye burns, glaucoma, cataract, intraocular hemorrhage, diabetic retinopathy, and others). So, one of the perspective approaches for the treatment of eye inflammations accompanying such diseases is the use of antioxidants, in particular superoxide dismutase (SOD), in particular. Unlike corticosteroids, non-specific anti-inflammatory drugs, antibiotics, immunomodulators used in the combined medical therapy against eye inflammations, possessing numerous side effects, the application of drugs based on SOD is the most harmless. SOD removes the superoxide radicals and prevents the formation of others, more dangerous: hydroxyl radicals and singlet oxygen. It is very important that SOD is practically nontoxic. However, only 5-10 % SOD containing drug in the form of eye drops penetrates through the cornea to the intraocular tissues because of the technical and clinical problems, such as solubility of the components and instability of drug solutions, limited efficacy and limited corneal/sclera permeability, elimination of the major part of drug solution via the nasolacrimal drainage system after instillation. Drug loaded polymeric nanoparticles can improve the efficacy of drug delivery into the eye by overcoming corneal/sclera diffusion barrier, enhancing bioavailability and biocompatibility. The use of drug-containing nanoparticles can also decrease the dose of the drug and diminish side effects. In this study we demonstrate the advantages of topical instillations of superoxide dismutase 1 (SOD1) in the form of complexes ad conjugates with differently charged poly-electrolytes (so called “nanozymes” in the treatment of ocular inflammation. 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 (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.