Antiangiogenic effect of silicate nanoparticles on corneal neo-vascularisation induced by vascular endothelial growth factor

• Structure of corneal epithelial tight junctions and possible ways of SiNPs to penetrate this barrier.
• SiNP molecules cannot only block VEGF1 receptors but also effectively inhibit VEGF2 and VEGF3 receptors.

Corneal neo-vascularisation (NV) is a major sight-threatening condition and is caused by infections, degenerative disorders, inflammation and long-time contact lens wear. Corneal NV occurs when the balance between angiogenic and antiangiogenic factors is tipped towards angiogenic molecules. The abnormal vessels may decrease corneal clarity and vision, lead to inflammation and corneal scarring and worsen the prognosis of penetrating keratoplasty if needed.There is no definite therapeutic approach for cornea NV. Medical and surgical therapies used to reduce corneal NV include corticosteroids and non-steroidal anti-inflammatory agents, laser photocoagulation and needle diathermy. Many of these therapies not only have demonstrated limited success but also have associated adverse effects. Therefore, it is very necessary to provide novel therapeutic approaches. Recently, anti-vascular endothelial growth factor (anti-VGEF) therapy has been introduced for the management of corneal NV.Herein, we hypothesise the use of silicate nanoparticles (SiNPs) as a novel treatment for corneal NV. The penetration rate of SiNPs into the cornea is attributed to the size of nanoparticles. Therefore, different sizes of SiNPs (20–50 nm) would be prepared and loaded onto the tissue to determine corneal permeability towards them. In addition, SiNPs would be administered into the eye by topical, subconjunctival and corneal intrastromal injection and accumulate in newly formed vessels. This hypothesis has been developed by emphasising on the synthesis of SiNPs, characterisation of size-dependent properties and surface modification for the preparation of homogeneous nanocomposites, generated by a reverse micro-emulsion method. As the importance of concentration, shape and/or size of SiNPs could be key factors exerting their antiangiogenic effects, we suggest using 20–30-nm SiNPs to enhance their ability to penetrate into the corneal epithelium. We hypothesise that topical, subconjunctival and corneal intrastromal injections of SiNPs may effectively inhibit and treat corneal NV. Controlled experimental studies on rabbits are needed to test whether SiNPs are able to effectively inhibit VEGF-induced angiogenesis in every segment of the eye including anterior, middle (ciliary body and trabecular mesh work) and posterior segments.

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