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Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy.


ABSTRACT: We recently reported that the Ins2(Akita) mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2(Akita) mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP). The plasmid was compacted by CK30PEG10K into DNA nanoparticles (NPs) for in vivo delivery. Murine endothelial cell line, SVEC4-10, was first transfected with the plasmid. The mRNA levels of VEGF and VEGFR-2 were quantified by qRT-PCR and showed significant reduction in message expression compared with lipofectamine-transfected cells. Transfection of miR200-b suppressed the migration of SVEC4-10 cells. There was a significant inverse correlation between the level of expression of miR200-b and VEGFR-2. Intravitreal injection of miR200-b DNA NPs significantly reduced protein levels of VEGFR-2 as revealed by western blot and markedly suppressed angiogenesis as evaluated by fundus imaging in aged Ins2(Akita) mice even after 3months of post-injection. These findings suggest that NP-mediated miR200-b delivery has negatively regulated VEGFR-2 expression in vivo.

SUBMITTER: Mitra RN 

PROVIDER: S-EPMC5328608 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy.

Mitra Rajendra Narayan RN   Nichols Chance A CA   Guo Junjing J   Makkia Rasha R   Cooper Mark J MJ   Naash Muna I MI   Han Zongchao Z  

Journal of controlled release : official journal of the Controlled Release Society 20160611


We recently reported that the Ins2(Akita) mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2(Akita) mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b  ...[more]

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