Expression of MUC5AC in Ocular Surface Epithelial Cells Using Cationized Gelatin Nanoparticles

Zorzi, Giovanni K.; Contreras-Ruiz, Laura; Párraga, Jenny E.; López-García, Antonio; Bello, Rafael Romero; Diebold, Yolanda; Seijo, Begoña; Sánchez, Alejandro

doi:10.1021/mp200155t

Cited by 61 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most recently, Konat Zorzi et, al. has carried out a proof-of-concept experiment [30], in which nanoparticles are used to deliver MUC5AC expression plasmid into ocular surface epithelial cells to treat dry eye syndrome. Therefore, thorough understanding of the biological effect of mucin on the ocular surface will facilitate the improvement of these medications to treat dry eye syndrome.…”

Section: Discussionmentioning

confidence: 99%

Mucin Deficiency Causes Functional and Structural Changes of the Ocular Surface

Floyd

Evans

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

MUC5AC is the most abundant gel-forming mucin in the ocular system. However, the specific function is unknown. In the present study, a Muc5ac knockout (KO) mouse model was subject to various physiological measurements as compared to its wide-type (WT) control. Interestingly, when KO mice were compared to WT mice, the mean tear break up time (TBUT) values were significantly lower and corneal fluorescein staining scores were significantly higher. But the tear volume was not changed. Despite the lack of Muc5ac expression in the conjunctiva of KO mice, Muc5b expression was significantly increased in these mice. Corneal opacification, varying in location and severity, was found in a few KO mice but not in WT mice. The present results suggest a significant difference in the quality, but not the quantity, of tear fluid in the KO mice compared to WT mice. Dry eye disease is multifactorial and therefore further evaluation of the varying components of the tear film, lacrimal unit and corneal structure of these KO mice may help elucidate the role of mucins in dry eye disease. Because Muc5ac knockout mice have clinical features of dry eye, this mouse model will be extremely useful for further studies regarding the pathophysiology of the ocular surface in dry eye in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Mucin Deficiency Causes Functional and Structural Changes of the Ocular Surface

Floyd

Evans

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…However, highly cationic NPs tend to be associated with increased toxicity [153, 154], thus anionic polymers (e.g., chondroitin sulfate and dextran sulfate) can be incorporated into type A GNPs to neutralize the amine groups and improve the toxicity profile of the GNP [138]. This hybrid form of type A GNPs has been successfully used for the delivery of a plasmid DNA expressing MUC5AC (a type of gel-forming mucin secreted by conjunctiva goblet cells) to the cornea and conjunctiva in vivo as a treatment for dry-eye disease [155, 156]. However, the potential application of GNPs for retinal gene therapy has not been evaluated.…”

Section: Nps For Retinal Gene Therapymentioning

confidence: 99%

Nanoparticle-based technologies for retinal gene therapy

Adijanto

Naash

2015

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

For patients with hereditary retinal diseases, retinal gene therapy offers significant promise for the prevention of retinal degeneration. While adeno-associated virus (AAV)-based systems remain the most popular gene delivery method due to their high efficiency and successful clinical results, other delivery systems, such as non-viral nanoparticles (NPs) are being developed as additional therapeutic options. NP technologies come in several categories (e.g., polymer, liposomes, peptide compacted DNA), several of which have been tested in mouse models of retinal disease. Here, we discuss the key biochemical features of the different NPs that influence how they are internalized into cells, escape from endosomes, and are delivered into the nucleus. We review the primary mechanism of NP uptake by retinal cells and highlight various NPs that have been successfully used for in vivo gene delivery to the retina and RPE. Finally, we consider the various strategies that can be implemented in the plasmid DNA to generate persistent, high levels of gene expression.

show abstract

“…At 1 day post injection of chitosan DNA complex, it was observed that expression of CpG free pCpG-Luc plasmid DNA enhanced by 7.1, 116.8, and 76.8 folds, compared to commercially available gWiz-CMV-Luc, pPEI-CMV, and pPEI-UbC plasmid DNAs respectively, and demonstrated the development of effective vectors for corneal gene therapy 52 . Another biopolymer gelatin has also been investigated to deliver and significantly express mucin MUC5AC (responsible for dry eye syndrome) transgene into the cornea and conjunctiva in vivo 53 . In 2012, Delgado and colleagues reported the ocular gene therapy using solid lipid NPs (SLN) composed of biocompatible dextran, protamine, and a plasmid DNA (pCMS-EGFP or pCEP4-RS1) 54 .…”

Section: Ocular Gene Deliverymentioning

confidence: 99%

Nanoparticle‐motivated gene delivery for ophthalmic application

Mitra

Zheng

Han

2015

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Ophthalmic gene therapy is an intellectual and intentional manipulation of desired gene expression into the specific cells of an eye for the treatment of ophthalmic (ocular) genetic dystrophies and pathological conditions. Exogenous nucleic acids such as DNA, small interfering RNA (siRNA), micro RNA (miRNA), etc., are used for the purpose of managing expression of the desired therapeutic proteins in ocular tissues. The delivery of unprotected nucleic acids into the cells is limited due to exogenous and endogenous degradation modalities. Nanotechnology, a promising and sophisticated cutting edge tool, works as a protective shelter for these therapeutic nucleic acids. They are able to be safely delivered to the required cells in order to modulate anticipated protein expression. To this end, nanotechnology is seen as a potential and promising strategy in the field of ocular gene delivery. This review focused on current nanotechnology modalities and other promising non-viral strategies being used to deliver therapeutic genes in order to treat various devastating ocular diseases.

show abstract

Expression of MUC5AC in Ocular Surface Epithelial Cells Using Cationized Gelatin Nanoparticles

Cited by 61 publications

References 27 publications

Mucin Deficiency Causes Functional and Structural Changes of the Ocular Surface

Mucin Deficiency Causes Functional and Structural Changes of the Ocular Surface

Nanoparticle-based technologies for retinal gene therapy

Nanoparticle‐motivated gene delivery for ophthalmic application

Contact Info

Product

Resources

About