June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Prevention of photoreceptor apoptosis by a Cryptocyanine drug (NK-4), in RCS rats
Author Affiliations & Notes
  • Shihui Liu
    Ophthalmology, Okayama University Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Japan,Okayama, OKAYAMA, Japan
  • Toshihiko matsuo
    Ophthalmology, Okayama University Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Japan,Okayama, OKAYAMA, Japan
  • Mari Miyaji
    Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Japan
  • Osamu Hosoya
    Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Japan
  • Footnotes
    Commercial Relationships   Shihui Liu, None; Toshihiko matsuo, None; Mari Miyaji, None; Osamu Hosoya, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4945. doi:
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      Shihui Liu, Toshihiko matsuo, Mari Miyaji, Osamu Hosoya; Prevention of photoreceptor apoptosis by a Cryptocyanine drug (NK-4), in RCS rats. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4945.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : NK-4 (4,4’-[3-{2-(1-ethyl-4(1H)-quinolylidene)ethylidene}pro-penylene]bis(1- ethylquinolinium iodide)) (Lumin) has a variety of biological activities, such as anti-allergic properties, anti-microbial, macrophage-activating, and has a potential role to suppress the apoptosis of photoreceptor cells in RCS (Royal College of Surgeons) rats. The purpose of this study was to survey main pathways about anti-apoptotic mechanism exerted by NK-4, in RCS rat, an animal model of Retinitis Pigmentosa.

Methods : RCS rats were received intravitreous injection of 5 μL NK-4 solution (NK-4 powder dissolved in DMSO) at theconcentration of 0.1 mg/mL in the left eye of each rat, and 5 μL DMSO solution served as control in the right eye, at the age of 3 weeks and 4 weeks, with a 30-gauge-needle-attached Hamilton syringe. The rats were housed under a 12-hour light/dark cycle for 14 days, and then, sacrificed at the age of 5 weeks. The retinal tissue of each eye of the RCS rats were submitted to RNA-seq: the library was prepared by a kit (TruSeq Stranded), and transcriptome sequencing was performed on the Illumina platform. Functional and pathway enrichment analysis of differentially expressed genes were performed by Metascape and David software.

Results : Among all the transcripts of interest, the top up-regulated differentially expressed gene is Hmox1, Mt1, Ccl2, Sclc7a1, Atf5, Trib3, Nexn, Mt1, Casp4, Ccl2, Bfsp2, Rab11fip1, Cidea, Slc7a11, Bdh2, Mtap, Zc2hc1c, Stbd1, C1qtnf5. Functional and pathway enrichment analysis of up-regulated differentially expressed genes showed that hat anti-apoptosis efficacy of NK-4 in the retina of RCS rat, might be related to the pathway of negative regulation of neuron death, metal ion homeostasis, response to toxic substance, and pigment metabolic process.

Conclusions : In this study, we identified potential therapeutic effect of NK-4 in retina degeneration. These results contribute to the understanding of the molecular mechanisms involved in the neural anti-apoptotic role in RCS rats under NK-4 injection. We will plan to confirm the RNA-seq results by qRT-PCR in the next step.

This is a 2020 ARVO Annual Meeting abstract.

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