Downregulation of VEGF mRNA expression by triamcinolone acetonide acetate-loaded chitosan derivative nanoparticles in human retinal pigment epithelial cells

Zhou, Huaisheng; Yang, Liqun; Li, Huajie; Gong, Haijun; Cheng, Liangzheng; Zheng, Haisheng; Zhang, Liming; Lan, Yuqing

doi:10.2147/ijn.s29690

Cited by 11 publications

(5 citation statements)

References 37 publications

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“…Given the apparent role of inflammation in the pathogenesis of DR and DME, intravitreal steroids have been utilized for the treatment of DME. The mode of action is unclear, but it has been suggested to be through multiple mechanisms including their ability to inhibit expression of VEGF [ 146 , 147 ]. The effects of steroids on microglia under DR and DME conditions remain unknown; however, other ocular disease models are starting to elucidate the effects of intravitreal corticosteroid delivery on microglia.…”

Section: The Effects Of Diabetes Treatments On Microgliamentioning

confidence: 99%

The Role of Microglia in Diabetic Retinopathy

Grigsby¹,

Cardona

Pouw

et al. 2014

Journal of Ophthalmology

156

163

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There is growing evidence that chronic inflammation plays a role in both the development and progression of diabetic retinopathy. There is also evidence that molecules produced as a result of hyperglycemia can activate microglia. However the exact contribution of microglia, the resident immune cells of the central nervous system, to retinal tissue damage during diabetes remains unclear. Current data suggest that dysregulated microglial responses are linked to their deleterious effects in several neurological diseases associated with chronic inflammation. As inflammatory cytokines and hyperglycemia disseminate through the diabetic retina, microglia can change to an activated state, increase in number, translocate through the retina, and themselves become the producers of inflammatory and apoptotic molecules or alternatively exert anti-inflammatory effects. In addition, microglial genetic variations may account for some of the individual differences commonly seen in patient's susceptibility to diabetic retinopathy.

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Section: The Effects Of Diabetes Treatments On Microgliamentioning

confidence: 99%

The Role of Microglia in Diabetic Retinopathy

Grigsby¹,

Cardona

Pouw

et al. 2014

Journal of Ophthalmology

156

163

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“…While in-depth toxicity studies will be conducted in future, we observe no histological or functional signs of gross retinal toxicity or degeneration following subretinal delivery of GCS NPs. This is particularly important as unmodified chitosan in the eye has been shown to induce some toxic effects [28] (although other modified chitosans, such as deoxycholic acid-substituted chitosan were shown not be cytotoxic [29] ).…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of Glycol Chitosan DNA Nanoparticles for Retinal Gene Delivery

et al. 2013

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Given the number of monogenic ocular diseases and the number of non-monogenic degenerative ocular diseases for which gene therapy has been considered as a treatment, the development of effective therapeutic delivery strategies for DNA is a critical research goal. Here we generate, characterize, and evaluate non-viral nanoparticles composed of glycol chitosan (GCS) and plasmid DNA (pDNA). We show that these particles are stable, do not aggregate in saline, are resistant to DNases, and have a hydrodynamic diameter of ∼250 nm. We further show that the plasmid in these NPs maintains its proper conformation and can be released and expressed inside the cell. To determine whether these NPs would be suitable for intraocular use, pDNA carrying the ubiquitously expressed CBA-eGFP expression cassette was compacted and subretinally injected into adult WT albino mice. At post-injection (PI) day 14, we observe substantial GFP expression exclusively in the retinal pigment epithelium (RPE) in eyes treated with GCS NPs but not in uncompacted pDNA or vehicle (saline) treated eyes. We observe no signs of gross retinal toxicity and at PI-30 days, there is no difference in electroretinogram function between GCS NP-, pDNA-, or vehicle-treated eyes. These results suggest that with further development GCS NPs may be a useful addition to our available repertoire of genetic therapies for the treatment of RPE-associated diseases.

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“…In this study, the conjugated nanochitosan peptide showed evidence of tyrosine kinase activity as indicated by fluorescent signals under the confocal microscope, while nanochitosan or peptide alone did not show such activity. Zhou et al ( 42 ) designed a study for investigating the downregulation of mRNA expression of VEGF by triamcinolone acetonide acetate (TAA)-loaded chitosan nanoparticles in human retinal pigment epithelial cells. The study demonstrated that TAA/loaded deoxycholic acid (DA)-modified chitosan nanoparticles had a downregulating effect on VEGF mRNA expression in human retinal pigment epithelial cells with low cytotoxicity; these are beneficial characteristics suggesting the suitability of these chitosan-derived nanoparticles to be developed into therapeutics for diabetic retinopathy.…”

Section: Current Status Of Gene Therapy Of Ocular Diseasementioning

confidence: 99%

Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review)

Wan

Liu

2015

Molecular Medicine Reports

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The eye is an ideal target organ for gene therapy as it is easily accessible and immune-privileged. With the increasing insight into the underlying molecular mechanisms of ocular diseases, gene therapy has been proposed as an effective approach. Successful gene therapy depends on efficient gene transfer to targeted cells to prove stable and prolonged gene expression with minimal toxicity. At present, the main hindrance regarding the clinical application of gene therapy is not the lack of an ideal gene, but rather the lack of a safe and efficient method to selectively deliver genes to target cells and tissues. Ultrasound-targeted microbubble destruction (UTMD), with the advantages of high safety, repetitive applicability and tissue targeting, has become a potential strategy for gene- and drug delivery. When gene-loaded microbubbles are injected, UTMD is able to enhance the transport of the gene to the targeted cells. High-amplitude oscillations of microbubbles act as cavitation nuclei which can effectively focus ultrasound energy, produce oscillations and disruptions that increase the permeability of the cell membrane and create transient pores in the cell membrane. Thereby, the efficiency of gene therapy can be significantly improved. The UTMD-mediated gene delivery system has been widely used in pre-clinical studies to enhance gene expression in a site-specific manner in a variety of organs. With reasonable application, the effects of sonoporation can be spatially and temporally controlled to improve localized tissue deposition of gene complexes for ocular gene therapy applications. In addition, appropriately powered, focused ultrasound combined with microbubbles can induce a reversible disruption of the blood-retinal barrier with no significant side effects. The present review discusses the current status of gene therapy of ocular diseases as well as studies on gene therapy of ocular diseases meditated by UTMD.

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Downregulation of VEGF mRNA expression by triamcinolone acetonide acetate-loaded chitosan derivative nanoparticles in human retinal pigment epithelial cells

Cited by 11 publications

References 37 publications

The Role of Microglia in Diabetic Retinopathy

The Role of Microglia in Diabetic Retinopathy

Synthesis and Characterization of Glycol Chitosan DNA Nanoparticles for Retinal Gene Delivery

Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review)

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