Chen Tan,Fan Jia,Peng Zhang,Xinghuai Sun,Yunsheng Qiao,Xueli Chen,Youxiang Wang,Junyi Chen,Yuan Lei
The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine–polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.
The conjunctiva covers the largest area of ocular surface and is responsible for tear balance and clear vision. After trauma or surgery, the conjunctiva is prone to scarring and contracture. Transplantation with suture often implies numerous complications, such as inflammation, suture erosion, granuloma. And the suture needs to be removed, which means a secondary trauma. In this study, a bioadhesive hydrogel (GMO) for sutureless conjunctival transplantation was developed based on a semi-interpenetrating polymer network (sIPN) consisting of gelatin methacrylate (GelMA) and oxidized hyaluronic acid (OHA). The maximum adhesion strength was 157 ± 17 kPa, and the burst pressure was 357 ± 29 kPa, which was 15 times higher than the human intraocular pressure (IOP). GMO bioadhesive hydrogel significantly improved surgical efficiency and secured the collagen scaffold firmly to a rabbit conjunctival defect. The sutureless transplantation approach revealed the promoted tissue repair without scar. In conclusion, GMO bioadhesive may be an attractive alternative to suture for ocular surface reconstruction by avoiding suture-related complications and improving clinical outcome. Statement of significance Conjunctival tissue is prone to scarring and contracture after trauma, and surgery with sutures often implies numerous complications. In this study, the ocular surface reconstruction was achieved by sutureless transplantation of conjunctival scaffold using bioadhesive hydrogel. The prepared GMO bioadhesive based on the semi-interpenetrating network of gelatin methacrylate (GelMA) and oxidized hyaluronic acid (OHA) had favorable adhesion and mechanical properties . The sutureless transplantation approach significantly improved the operation efficiency, avoided suture-related complications, and promoted the regeneration of conjunctiva. This study highlights the great potential of the sutureless repair strategy for clinical application in ocular surface reconstruction.
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