July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Development of a Pde6b Gene Knockout Rat Model for Studies of Degenerative Retinal Diseases
Author Affiliations & Notes
  • Joonhyung Yeo
    Department of Ophthalmology, Asan Medical Center, Seoul, Korea, Seoul, Korea (the Republic of)
  • Bok Kyoung Jung
    Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (the Republic of)
  • Young Hoon Sung
    Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (the Republic of)
  • In-Jeoung Baek
    Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (the Republic of)
  • Joo Yong Lee
    Department of Ophthalmology, Asan Medical Center, Seoul, Korea, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Joonhyung Yeo, None; Bok Kyoung Jung, None; Young Hoon Sung, None; In-Jeoung Baek, None; Joo Yong Lee, None
  • Footnotes
    Support  HI15C2599
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 447. doi:
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      Joonhyung Yeo, Bok Kyoung Jung, Young Hoon Sung, In-Jeoung Baek, Joo Yong Lee; Development of a Pde6b Gene Knockout Rat Model for Studies of Degenerative Retinal Diseases. Invest. Ophthalmol. Vis. Sci. 2019;60(9):447.

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

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Abstract

Purpose : To describe the phenotypes of a newly developed Pde6b-deficient rat model of retinal degeneration.

Methods : Pde6b knockout rats were produced by CRISPR-Cpf1 technology. Pde6b knockout rats were evaluated for ocular abnormalities by comparison with wild-type eyes; eyes were imaged by using fundus photography and optical coherence tomography (OCT), and stained by hematoxylin and eosin (H&E) and TUNEL assay. Finally, eyes were functionally assessed by electroretinograms (ERG).

Results : Pde6b knockout rats exhibited visible photoreceptor degeneration at 3 weeks of postnatal age. The fundus appearance of mutants was notable for pigmentary changes, vascular attenuation with an irregular vascular pattern, and outer retinal thinning, which resembled retinitis pigmentosa (RP) in humans. OCT showed profound retinal thinning in Pde6b knockout rats; the outer nuclear layer (ONL) was significantly thinner in Pde6b knockout rats, with relative preservation of the inner retina at 3 weeks of postnatal age. H&E staining confirmed extensive degeneration of the ONL, beginning at 3 weeks of postnatal age; no ONL remained in the retina by 16 weeks of postnatal age. Retinal sections of Pde6b knockout rats were highly positive for TUNEL, specifically in the ONL. In ERGs, Pde6b knockout rats showed no detectable a- or b-waves at 8 weeks of postnatal age.

Conclusions : The Pde6b knockout rat exhibits photoreceptor degeneration. It may provide a better model for experimental therapy for RP because of its slower progression and larger anatomical architecture than the corresponding mouse model. Further studies in this rat model may yield insights into effective therapies for human RP.

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

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