Efficient ocular delivery of siRNA via pH-sensitive vehicles for corneal neovascularization inhibition

Cao, Xun; Wang, Changrong; Deng, Zhennv; Ye, Zhong; Chen, Hao

doi:10.1016/j.ijpx.2023.100183

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…[ 115 116 ] Ocular delivery of small interfering RNA via pH-sensitive vehicles had comparable efficacy to that of ranibizumab. [ 117 ] The only Phase III clinical gene therapy study is that of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, which has been shown to inhibit CoNV and reduce the need for transplantation in patients with keratitis. [ 118 ] Aganirsen has since been granted an Orphan Drug Designation by the US Food and Drug Administration for the prevention of corneal graft rejection in 2016.…”

Section: Methodsmentioning

confidence: 99%

Management of corneal neovascularization: Current and emerging therapeutic approaches

Wu,

Chan,

Lim

et al. 2024

Indian Journal of Ophthalmology

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Corneal neovascularization (CoNV) is a sight-threatening condition affecting an estimated 1.4 million people per year, and the incidence is expected to rise. It is a complication of corneal pathological diseases such as infective keratitis, chemical burn, corneal limbal stem cell deficiency, mechanical trauma, and immunological rejection after keratoplasties. CoNV occurs due to a disequilibrium in proangiogenic and antiangiogenic mediators, involving a complex system of molecular interactions. Treatment of CoNV is challenging, and no therapy thus far has been curative. Anti-inflammatory agents such as corticosteroids are the mainstay of treatment due to their accessibility and well-studied safety profile. However, they have limited effectiveness and are unable to regress more mature neovascularization. With the advent of advanced imaging modalities and an expanding understanding of its pathogenesis, contemporary treatments targeting a wide array of molecular mechanisms and surgical options are gaining traction. This review aims to summarize evidence regarding conventional and emerging therapeutic options for CoNV.

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Section: Methodsmentioning

confidence: 99%

Management of corneal neovascularization: Current and emerging therapeutic approaches

Wu,

Chan,

Lim

et al. 2024

Indian Journal of Ophthalmology

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“…The inhibitory effect of TPPA-siVEGFA on corneal neovascularization was comparable to that of ranibizumab. Delivering siRNA to the ocular environment via pH-sensitive polycations provides a novel strategy for effectively inhibiting corneal neovascularization [113]. siRNAs can be engineered to target other key genes responsible for producing angiogenesis-related factors, such as PDGF and FGF.…”

Section: Small Interfering Rna (Sirna) Gene Therapymentioning

confidence: 99%

Available Therapeutic Options for Corneal Neovascularization: A Review

Drzyzga,

Śpiewak,

Dorecka

et al. 2024

IJMS

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Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-β) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-β-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

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Efficient ocular delivery of siRNA via pH-sensitive vehicles for corneal neovascularization inhibition

Cited by 2 publications

References 45 publications

Management of corneal neovascularization: Current and emerging therapeutic approaches

Management of corneal neovascularization: Current and emerging therapeutic approaches

Available Therapeutic Options for Corneal Neovascularization: A Review

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