UMMS Affiliation

Department of Ophthalmology and Visual Sciences

Publication Date

2019-04-05

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Eye Diseases | Genetic Phenomena | Genetics and Genomics

Abstract

X-linked retinitis pigmentosa 2 (XLRP2) patients and Rp2 (null) mice exhibit severe cone photoreceptor degeneration. However, due to the paucity of cones in mammalian model systems, it is not clear how cones respond to the loss of RP2. Here we have used the Nrl(-/-) mice, which develop a rodless and short wavelength (S) opsin-containing cone-only retina, to generate Rp2 (null)::Nrl(-/-) double knock out (Rp2-DKO) mice. We found that the ciliary axoneme and the outer segments (OSs) of the cones were significantly longer with disorganized membrane infoldings as compared to the Nrl(-/-) mice. Additionally, we found misregulation in the expression of the genes related to ophthalmic disease, cell trafficking, and stress-response in the Rp2-DKO mice prior to the onset of cone degeneration. Surprisingly, the loss of RP2 did not affect progressive photoreceptor dysfunction of the Nrl(-/-) mice and the trafficking of S opsin. Our data suggest that RP2 is a negative regulator of cone OS length but does not affect S-opsin trafficking and S-cone function. Our studies also provide a cone-only platform to design cone-targeted therapeutic strategies for X-linked RP2.

Keywords

cilia, ciliopathies, cone, opsin, photoreceptors, retinal degeneration

Rights and Permissions

Copyright © 2019 Li, Rao and Khanna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version

10.3389/fgene.2019.00323

Source

Front Genet. 2019 Apr 5;10:323. doi: 10.3389/fgene.2019.00323. eCollection 2019. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in genetics

Related Resources

Link to Article in PubMed

PubMed ID

31024631

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.