The Xaliproden Nanoscale Zirconium-Porphyrin Metal-Organic Framework (XAL-NPMOF) Promotes Photoreceptor Regeneration Following Oxidative and Inflammatory Insults

Yajie Wang,1,* Bo Yuan,2,* Wei Liu,3,* Jianlin Cui,2 Xueyan Zhou,2 Liyun Yuan,2 Zihao Deng,4 Yuhao Li,5,6 Xiaoyong Yuan1,2 1Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Tianjin Zhonghe Gene Technology Limited Company, Tianjin, People’s Republic of China; 4Cancer Center, Capital Medical University, Beijing, People’s Republic of China; 5Central Laboratory, Xuanwu Hospital Capital Medical University, Beijing Geriatric Medical Research Center, Beijing, People’s Republic of China; 6Optometry Institute, Nankai University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyong Yuan, Tianjin Eye Hospital, Tianjin key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, People’s Republic of China, Email [email protected] Yuhao Li, Central Laboratory, Xuanwu Hospital Capital Medical University, Beijing Geriatric Medical Research Center, Beijing, People’s Republic of China, Email [email protected]: Age-related macular degeneration (AMD) is becoming the leading cause of blindness in the aged population. The death of photoreceptors is the principal event which is lack of curative treatment. Xaliproden, a highly selective synthetic 5-OH-tryptamine (5HT) 1A receptor agonist, has the neuroprotective potential. However, its application has been limited by the insoluble formulation, low utilization efficiency and side effects caused by systemic administration.Methods: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was used as a skeleton and loaded with xaliproden (XAL) to prepare a novel kind of nanoparticle, namely, XAL-NPMOF. The human umbilical vein endothelial cells, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of XAL-NPMOF both in vitro and in vivo. A photoreceptor degeneration model was generated by intense light injury in adult zebrafish and XAL-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration, inflammatory response and visual function were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and optomotor response analysis.Results: Following a single XAL-NPMOF intraocular injection, the injured retina underwent the faster photoreceptor regeneration with a recovery of visual function via promoting cell proliferation, suppressing the inflammatory responses and increasing the expression of antioxidases.Conclusion: As an amplifier, NPMOF can enhance the anti-inflammatory efficacy and neuroprotective effect of xaliproden. XAL-NPMOF could be a novel and convenient option for the treatment of AMD.Keywords: nanoscale zirconium-porphyrin metal-organic framework, xaliproden, photoreceptor, anti-inflammatory effect, regeneration