The Effect of Cyanine Dye NK-4 on Photoreceptor Degeneration in a Rat Model of Early-Stage Retinitis Pigmentosa
| Autor: | Toshihiko Matsuo, Shihui Liu, Osamu Hosoya, Mary Miyaji |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
retina antioxidant genetic structures Pharmaceutical Science Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacy and materia medica retinitis pigmentosa Drug Discovery Retinitis pigmentosa medicine NK-4 Outer nuclear layer Metal ion homeostasis Retina TUNEL assay Pigment metabolic process apoptosis Retinal medicine.disease photoreceptor eye diseases Cell biology RS1-441 030104 developmental biology medicine.anatomical_structure chemistry 030221 ophthalmology & optometry Molecular Medicine Medicine sense organs RNA-seq Neuron death metabolism |
| Zdroj: | Pharmaceuticals Pharmaceuticals, Vol 14, Iss 694, p 694 (2021) Volume 14 Issue 7 |
| ISSN: | 1424-8247 |
| Popis: | The present study aimed to evaluate the effects of NK-4 on the apoptosis of photoreceptors in a rat model of retinitis pigmentosa and explore the mechanism underlying anti-apoptosis activity. The Royal College of Surgeons (RCS) rats received an intravitreous injection of NK-4 solution in the left eye and vehicle control in the right eye. Apoptosis was detected by TUNEL method in frozen sections of the eyes. The retinal tissues of the rats were dissected for RNA-seq analysis. Functional and pathway enrichment analyses of differentially expressed genes (DEGs) were performed by using Metascape and DAVID software. The expression levels of DEGs were confirmed by real-time quantitative PCR (RT-qPCR). The number of apoptotic cells decreased in the outer nuclear layer (ONL) and the thickness of the ONL was significantly thicker in the retina of NK-4-injected eyes, compared with control eyes. Five DEGs were identified by RNA-seq analysis, and Hmox1, Mt1, Atf5, Slc7a11, and Bdh2 were confirmed to be up-regulated by RT-qPCR. Functional and pathway enrichment analysis of the up-regulated genes showed that anti-apoptosis effects of NK-4 in the retina of RCS rats may be related to the pathways of metal ion homeostasis, negative regulation of neuron death, response to toxic substance, and pigment metabolic process. We found a potential mechanism of NK-4, providing a new viewpoint for the development of more therapeutic uses of NK-4 in the future. |
| Databáze: | OpenAIRE |
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