Abstract
Purpose :
To describe the development of a novel Pde6b-knockout Long–Evans (LE Pde6b KO) rat model with melanin-pigmentated retinal pigment epithelial (RPE) cells that recapitulates key features of human retinitis pigmentosa (RP).
Methods :
First, Pde6b-knockout Sprague–Dawley rats was generated with the CRISPR-Cpf1 system. After, the LE rat was back-crossed over 5 generations to develop the pigmented LE Pde6b KO strain.
Results :
Interestingly, LE Pde6b KO displayed well-developed bone-spicule pigmentation; a hallmark of fundus in patients with RP which cannot be observed in nonpigmented albino rats. Moreover, the rat model showed progressive thinning of the retina, which was evident by intravital imaging with optical coherence tomography. Histologically, significant atrophy was observed in the outer nuclear layer. Functionally, LE Pde6b KO presented a marked decrease of amplitude level during electroretinogram testing, demonstrating significant loss of visual function.
Conclusions :
The mentioned findings suggest that the LE Pde6b KO model robustly recapitulates the hallmark phenotype of RP. We believe that the LE Pde6b KO model may be used effectively for preclinical translational research to further study retinal degeneration.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.