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 language | English |
|---|---|
| Pages (from-to) | 1519-1526 |
| Number of pages | 8 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 60 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2019 Apr |
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All Science Journal Classification (ASJC) codes
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
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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 journal › Article
TY - JOUR
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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UR - http://www.scopus.com/inward/citedby.url?scp=85065093108&partnerID=8YFLogxK
U2 - 10.1167/iovs.18-25556
DO - 10.1167/iovs.18-25556
M3 - Article
C2 - 31009522
AN - SCOPUS:85065093108
VL - 60
SP - 1519
EP - 1526
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 5
ER -