July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Key pathways and genes influenced by a drug, NK-4, in RCS rats
Author Affiliations & Notes
  • Shihui Liu
    Ophthalmology, Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan
  • Toshihiko Matsuo
    Ophthalmology, Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan
  • Mary Miyaji
    Medical Neurobiology, Graduate School of Medicine, Dentistry, and Pharmaceutical, Okayama University, Okayama, Japan
  • Osamu Hosoya
    Medical Neurobiology, Graduate School of Medicine, Dentistry, and Pharmaceutical, Okayama University, Okayama, Japan
  • Footnotes
    Commercial Relationships   Shihui Liu, None; Toshihiko Matsuo, None; Mary Miyaji, None; Osamu Hosoya, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4478. doi:
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    • Get Citation

      Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya; Key pathways and genes influenced by a drug, NK-4, in RCS rats. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4478.

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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 anticancer, macrophage-activating, antimicrobialproperties, and has a potential role in inhibiting the apoptosis of photoreceptor cells in retinal dystrophic RCS (Royal College of Surgeons) rats (Liu S, et al. Invest. Ophthalmol. Vis. Sci.. 2017; 58(8):277. doi:). The aim of this study was to investigate gene signatures about anti-apoptotic mechanism exerted by Lumin, and to reveal their potential mechanisms in RCS rat, a model of retinitis pigmentosa.

Methods : RCS rats received intravitreous injection of 5 μL solution at the concentration of 0.1 mg/mL Lumin dissolved in DMSO, at the age of 3 weeks and 4 weeks, in the left eye of each rat, with a 30-gauge-needle-attached Hamilton syringe. DMSO injection in the same volume served as control in the right eye of each rat. The rats were housed under a 12-hour light/dark cycle for 14 days, and then sacrificed at the age of 5 weeks. The neuroretinal tissue of each RCS rats' eye was subjected to RNA-Seq: the library was prepared by a kit (TruSeq RNA Sample Prep Kit v2), and transcriptome sequencing was performed on the platform of cBOT and HiSeq2500 (Illumina).

Results : In total, 96 transcripts were chosen as meaningful genes in the presence of Lumin, including 15 up-regulated genes and 37 down-regulated genes. Among these transcripts of interest, the top gene in the up-regulated differentially expressed gene was Hmox1, and the top 9 genes in the down-regulated differentially expressed genes were Cryaa, Cryba1, Cryba4, Crybb3, Cryga, Crygb, Crygd, Fhit, and Mapre2.

Conclusions : Anti-apoptosis efficacy in the dystrophic retinal tissue of RCS rats might berelated to retinal crystallins, according to the list of down-regulated differentially expressed genes. The differentially expressed genes which were identified in this study would give a key for understanding molecular mechanisms underlying the role of Lumin in neural anti-apoptotic role in RCS rats. The RNA-Seq results will be validated by qRT-PCR in the next step.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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