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Journal Articles Pharmaceutics Year : 2020

Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration

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Dysregulation of iron metabolism is observed in animal models of retinitis pigmentosa (RP) and in patients with age-related macular degeneration (AMD), possibly contributing to oxidative damage of the retina. Transferrin (TF), an endogenous iron chelator, was proposed as a therapeutic candidate. Here, the efficacy of TF non-viral gene therapy based on the electrotransfection of pEYS611, a plasmid encoding human TF, into the ciliary muscle was evaluated in several rat models of retinal degeneration. pEYS611 administration allowed for the sustained intraocular production of TF for at least 3 and 6 months in rats and rabbits, respectively. In the photo-oxidative damage model, pEYS611 protected both retinal structure and function more efficiently than carnosic acid, a natural antioxidant, reduced microglial infiltration in the outer retina and preserved the integrity of the outer retinal barrier. pEYS611 also protected photoreceptors from N-methyl-N-nitrosourea-induced apoptosis. Finally, pEYS611 delayed structural and functional degeneration in the RCS rat model of RP while malondialdehyde (MDA) ocular content, a biomarker of oxidative stress, was decreased. The neuroprotective benefits of TF non-viral gene delivery in retinal degenerative disease models further validates iron overload as a therapeutic target and supports the continued development of pEY611 for treatment of RP and dry AMD.
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Dates and versions

inserm-02980529 , version 1 (27-10-2020)



Karine Bigot, Pauline Gondouin, Romain Bénard, Pierrick Montagne, Jenny Youale, et al.. Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration. Pharmaceutics, 2020, 12 (9), pp.836. ⟨10.3390/pharmaceutics12090836⟩. ⟨inserm-02980529⟩
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