Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases

Joon Hyung Yeo, Bok Kyoung Jung, Heuiran Lee, In Jeoung Baek, Young Hoon Sung, Hae Sol Shin, Hong Kyung Kim, Kyoung Yul Seo, Joo Yong Lee

Research output: Contribution to journalArticle

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 using fundus photography and optical coherence tomography (OCT), stained by hematoxylin and eosin (H&E), and examined by TUNEL assay. Finally, eyes were functionally assessed by electroretinograms (ERGs). 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 anatomic architecture than the corresponding mouse model. Further studies in this rat model may yield insights into effective therapies for human RP.

Original languageEnglish
Pages (from-to)1519-1526
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume60
Issue number5
DOIs
Publication statusPublished - 2019 Apr

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Retinal Diseases
Gene Knockout Techniques
Retinitis Pigmentosa
In Situ Nick-End Labeling
Optical Coherence Tomography
Blood Vessels
Retina
Clustered Regularly Interspaced Short Palindromic Repeats
Eye Abnormalities
Retinal Degeneration
Investigational Therapies
Photography
Hematoxylin
Eosine Yellowish-(YS)
Staining and Labeling
Technology
Phenotype

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Yeo, J. H., Jung, B. K., Lee, H., Baek, I. J., Sung, Y. H., Shin, H. S., ... Lee, J. Y. (2019). Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases. Investigative Ophthalmology and Visual Science, 60(5), 1519-1526. https://doi.org/10.1167/iovs.18-25556
Yeo, Joon Hyung ; Jung, Bok Kyoung ; Lee, Heuiran ; Baek, In Jeoung ; Sung, Young Hoon ; Shin, Hae Sol ; Kim, Hong Kyung ; Seo, Kyoung Yul ; Lee, Joo Yong. / Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases. In: Investigative Ophthalmology and Visual Science. 2019 ; Vol. 60, No. 5. pp. 1519-1526.
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Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases. / Yeo, Joon Hyung; Jung, Bok Kyoung; Lee, Heuiran; Baek, In Jeoung; Sung, Young Hoon; Shin, Hae Sol; Kim, Hong Kyung; Seo, Kyoung Yul; Lee, Joo Yong.

In: Investigative Ophthalmology and Visual Science, Vol. 60, No. 5, 04.2019, p. 1519-1526.

Research output: Contribution to journalArticle

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T1 - Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases

AU - Yeo, Joon Hyung

AU - Jung, Bok Kyoung

AU - Lee, Heuiran

AU - Baek, In Jeoung

AU - Sung, Young Hoon

AU - Shin, Hae Sol

AU - Kim, Hong Kyung

AU - Seo, Kyoung Yul

AU - Lee, Joo Yong

PY - 2019/4

Y1 - 2019/4

N2 - 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 using fundus photography and optical coherence tomography (OCT), stained by hematoxylin and eosin (H&E), and examined by TUNEL assay. Finally, eyes were functionally assessed by electroretinograms (ERGs). 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 anatomic architecture than the corresponding mouse model. Further studies in this rat model may yield insights into effective therapies for human RP.

AB - 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 using fundus photography and optical coherence tomography (OCT), stained by hematoxylin and eosin (H&E), and examined by TUNEL assay. Finally, eyes were functionally assessed by electroretinograms (ERGs). 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 anatomic architecture than the corresponding mouse model. Further studies in this rat model may yield insights into effective therapies for human RP.

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