Abstract
Background
Photoreceptor degeneration is one of the most refractory oculopathy in the world, leading to vision loss in severe cases. Methyprednisolone is one of the most commonly prescribed medications for the treatment of retinal degenerative diseases, either by oral administration or repeated intraocular injections. However, the efficacy was unsatisfactory due to its systemic or local side effects and short retention time within the retina.
Methods
Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was synthesized and characterized. The biotoxicity and imaging capability of NPMOF were evaluated using zebrafish embryos and larvae. NPMOF was then used as a skeleton and loaded with methylprednisolone (MPS) to prepare a novel kind of nanoparticle, MPS-NPMOF. Photoreceptor degeneration was induced by high-intensity light exposure in adult zebrafish. MPS-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration and its underlying mechanism were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and behavioral test.
Results
NPMOF not only had low biotoxicity but also emitted bright fluorescence. Following a single MPS-NPMOF intraocular injection, the injured retina exhibited the faster photoreceptor regeneration with better visual function by promoting the cell proliferation.
Conclusion
NPMOF is an ideal carrier and could be applied in tracking and delivering medications. By intraocular injection, the novel drug delivery system, MPS-NPMOF, accomplishes the sustained release of drug and plays a therapeutic role in photoreceptor degeneration.
Acknowledgments
This work was supported by Chinese National Natural Science Foundation (No. 81671179 and 81971739), the National Key R&D Program of China (No. 2017YFA0103201), Tianjin Talent Innovation Group of 131, Bureau of Personnel, CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-1-017 & 2017-I2M-B&R-13), and the Fundamental Research Funds for the Central Universities (Nankai University No. 63191154). The authors thank Dr. Shaohua Yao (State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University) for providing transgenic zebrafish Tg (lysC:EGFP).
Disclosure
The authors report no conflicts of interest in this work.