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

• Main Authors: C. Henrique Alves, Nanda Boon, Aat A. Mulder, Abraham J. Koster, Carolina R. Jost, Jan Wijnholds
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: International Journal of Molecular Sciences
• Subjects: crumbs complex; crumbs homolog-1; Leber congenital amaurosis; photoreceptors; retina; retinal degeneration; retinitis pigmentosa; rod photoreceptors
• Online Access: https://www.mdpi.com/1422-0067/20/17/4069

Variations in the Crumbs homolog-1 (<i>CRB1</i>) 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 <i>Crb1</i>-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.