The Xaliproden Nanoscale Zirconium-Porphyrin Metal-Organic Framework (XAL-NPMOF) Promotes Photoreceptor Regeneration
Yajie Wang1, Bo Yuan2, Wei Liu3
1Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, People's Republic of China.
Background:
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.
