CRB2 Loss in Rod Photoreceptors Is Associated with Progressive Loss of Retinal Contrast Sensitivity

International Journal of Molecular Sciences

Jan Wijnholds¹  AbrahamJ. Koster¹  CarolinaR. Jost²  AatA. Mulder²  Nanda Boon³  C.Henrique Alves³ 

[1] Chemical Biology, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands;;Department of Cell &Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands;

关键词: crumbs complex;    crumbs homolog-1;    Leber congenital amaurosis;    photoreceptors;    retina;    retinal degeneration;    retinitis pigmentosa;    rod photoreceptors;   

DOI  :  10.3390/ijms20174069

来源: DOAJ

【 摘 要 】

Variations in the Crumbs homolog-1 (CRB1) gene are associated with a wide variety of autosomal recessive retinal dystrophies, including early onset retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). CRB1 belongs to the Crumbs family, which in mammals includes CRB2 and CRB3. Here, we studied the specific roles of CRB2 in rod photoreceptor cells and whether ablation of CRB2 in rods exacerbates the Crb1-disease. Therefore, we assessed the morphological, retinal, and visual functional consequences of specific ablation of CRB2 from rods with or without concomitant loss of CRB1. Our data demonstrated that loss of CRB2 in mature rods resulted in RP. The retina showed gliosis and disruption of the subapical region and adherens junctions at the outer limiting membrane. Rods were lost at the peripheral and central superior retina, while gross retinal lamination was preserved. Rod function as measured by electroretinography was impaired in adult mice. Additional loss of CRB1 exacerbated the retinal phenotype leading to an early reduction of the dark-adapted rod photoreceptor a-wave and reduced contrast sensitivity from 3-months-of-age, as measured by optokinetic tracking reflex (OKT) behavior testing. The data suggest that CRB2 present in rods is required to prevent photoreceptor degeneration and vision loss.

【 授权许可】

Unknown