| RE F-002 |
| Development of a Pde6b Gene Knockout Rat Model for Studies of Degenerative Retinal Diseases |
| (1) Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine
(2) Asan Institute for Life Sciences, Asan Medical Center |
| Joon Hyung Yeo, Bok Kyoung Jung, Young Hoon Sung, In-Jeoung Baek, Joo Yong Lee |
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목적 : To describe the phenotypes of a newly developed Pde6b-deficient rat model of retinal degeneration.
방법 : Pde6b knockout (KO) rats were produced by CRISPR-Cpf1 technology. KO 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).
결과 : KO rats exhibited visible photoreceptor degeneration at postnatal week (P) 3. The fundus appearance of mutants was notable for vascular attenuation with an irregular vascular pattern. OCT showed profound retinal thinning in KO rats; the outer nuclear layer (ONL) was significantly thinner in KO rats, with relative preservation of the inner retina at P3. H&E staining confirmed extensive degeneration of the ONL, beginning at P3; no ONL remained by P16. Retinal sections of KO rats were highly TUNEL positive, specifically in the ONL. In ERGs, KO rats showed no detectable a- or b-waves at P8.
결론 : The Pde6b KO 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.
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