Phytic acid-loaded polyvinyl alcohol hydrogel promotes wound healing of injured corneal epithelium through inhibiting ferroptosis
Danni Gong,
Nianxuan Wu,
Huan Chen,
Weijie Zhang,
Chenxi Yan,
Chunlei Zhang,
Yao Fu,
Hao Sun
Affiliations
Danni Gong
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China
Nianxuan Wu
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China
Huan Chen
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China
Weijie Zhang
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China
Chenxi Yan
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China
Chunlei Zhang
Institute of Nano Biomedicine and Engineering, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China; Corresponding author. Institute of Nano Biomedicine and Engineering, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, No.800, Dongchuan Road, Minhang District, Shanghai, 200240, China.
Yao Fu
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China; Corresponding author. Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
Hao Sun
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China; Corresponding author. Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
As the important barrier of intraocular tissue, cornea is easy to suffer various kinds of injuries. Among them, acute alkali burn is a thorny ophthalmic emergency event, which can lead to corneal persistent epithelial defects, ulcers, and even perforation. Ferroptosis, a mode of regulatory cell death, has been found to play a key role in the process of corneal alkali burn, of which lipid peroxidation and intracellular iron levels are considered to be the possible therapeutic targets. To seek new effective treatments, the study herein focused on the occurrence of oxidative stress and ferroptosis in corneal alkali burn, exploring the role of phytic acid (PA), a natural small molecule with both antioxidant and iron chelating capacity, in the repair of corneal epithelial injury. The in vivo therapeutic results showed that PA eyedrops treatment promoted the recovery of corneal morphology and function, and in vitro experiments proved that PA prompted the repair of oxidative stress induced-corneal epithelial injury through ferroptosis inhibition. In addition, better drug treatment effect could be achieved through hydrogel delivery and sustained release, and our in vivo experiments showed the superior therapeutic effects of PA delivered by PVA hydrogels with larger molecular weights on corneal injury. In summary, this study demonstrated the excellent effect of natural small molecule PA with antioxidant and high efficiency chelating ferrous ions on ferroptosis inhibition, and showed the outstanding application prospect of PVA/PA hydrogels in the treatment of corneal epithelial injury.
