Potential applications for RNAi to probe pathogenesis and develop new treatments for ocular disorders

Campochiaro, Peter A.

doi:10.1038/sj.gt.3302653

Cited by 98 publications

(67 citation statements)

References 34 publications

(26 reference statements)

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“…The technology of RNAi is an intriguing and powerful method of gene downregulation, which has been widely used to study gene function and target discovery. 29,55 siRNA can degrade mRNA, which has a complementary sequence to the siRNA by the RNAi mechanism. [56][57][58] In addition to siRNA, DNA vectors that transcribe siRNA or shRNA are also available to induce RNAi.…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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The aim of this study was to evaluate the possibility of poly (D, L-lactide-co-glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA) and to investigate its inhibitory efficacy on experimental choroidal neovascularization (CNV). We developed intravitreal administered, hypoxia-inducible factor 1a (HIF-1a) short hairpin RNA and green fluorescent protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1a NPs). CNV was induced by laser photocoagulation in 112 rats. The rats were then randomly assigned to be injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked pDNA, control pDNA NPs and pshHIF-1a NPs, respectively, and non-injection group was set as the control. Immunofluorescence staining, fluorescein fundus angiography and histologic analysis were performed to evaluate the inhibitory efficacy on CNV. The results showed that the expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks. The fluorescein leakage areas of CNV were significantly larger in the PBS, blank NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF-1a NPs group (Po0.01). The mean thickness of the CNV lesions in the intravitreally pshHIF1a NPs-treated group was significantly smaller than other groups (Po0.01). No signs of functional or ultrastructural destruction in retina were detected. Therefore, pshHIF-1a NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV.

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Section: Discussionmentioning

confidence: 99%

“…28 Using siRNA directed against VEGF or VEGF receptors in CNV animal models have also showed promising results. [29][30][31] Clinical trials involving RNAi targeting VEGF or its receptor through intravitreal injection delivery are currently underway. 32 However, generating sustained expression of the transgene remains a vexing problem.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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“…80 A plethora of in vivo studies to test this approach have been carried out in recent years, so far yielding at least one multicenter trial that aims to bring a specific corneal angiogenesis inhibitor into the ophthalmic clinic. 85 Future challenges include the achievement of successful delivery and stable expression of therapeutic genes.…”

Section: Discussionmentioning

confidence: 99%

“…78 It is worth stressing that despite similarities, vascular growth may slightly differ between distinct anatomic locations. 79,80 For instance, VEGFR-1 acts as a decoy receptor in the cornea, but induces neovascularisation in the retina, as shown by reduction of retinal neovascularisation upon experimental disruption of VEGFR-1. 81 Overall, the natural avascularity of the cornea makes it quite an atypical environment to study vascular development.…”

Section: Translational Aspects Of Corneal Angiogenesis and Clinical Ementioning

confidence: 99%

“…28 This approach has been taken into clinical testing for subfoveal choroidal neovascularisation, 80 with the anterior segment now striving to follow suit. Here, injection of an adenovirus vector encoding a soluble Tie-2 receptor inhibited neovascularisation in a mouse model of corneal injury.…”

Section: Future Therapies May Rely On Local Gene Therapy To Influencementioning

confidence: 99%

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Emerging techniques to treat corneal neovascularisation

Menzel‐Severing

2011

Eye

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Neovascularisation is a major cause of visual loss in a number of ophthalmic diseases. This review aims to outline the basic regulators of vessel growth in corneal neovascularisation. An understanding of the underlying principles of physiological and pathophysiological vascular development helps to appreciate current approaches to prevent or treat corneal neovascularisation. Options for future interventions will be discussed in the light of recent evidence provided by animal models of corneal neovascularisation.

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A 76-Year-Old Man With Macular Degeneration

Arroyo¹

2006

JAMA

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Potential applications for RNAi to probe pathogenesis and develop new treatments for ocular disorders

Cited by 98 publications

References 34 publications

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Emerging techniques to treat corneal neovascularisation

A 76-Year-Old Man With Macular Degeneration

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