Crb2 In Retinal Development - Part 2

Abstract

Purpose: : To assess the effects of Crb2 deficiency on retinal morphology and layer integrity as well as retinal function.

Methods: : Crb2-Chx10Cre conditional knock-out (Crb2 KO) mice were generated as described in Part 1, examined functionally and morphologically as presented here, and subsequently underwent histological analysis (part 1). The examination of retinal morphology and vasculature was performed with confocal scanning-laser ophthalmoscopy (SLO), and that of retinal layer composition with the Spectralis^TM spectral domain optical coherence tomography (OCT). The functional analysis was done in the same mice with Ganzfeld electroretinography (ERG) under both scotopic and photopic conditions. The data presented here include Crb2 KO mice at the age of 1, 3, 6 and 12 months and respective controls.

Results: : A progressive retinal degeneration was found in Crb2 KO mice based on SLO and OCT imaging. Initial changes in retinal layer structure were visible in OCT at 1-3 months of age. During the course of the disease, the outer retina underwent a significant thinning of up to a complete loss at about 12 months of age. At that stage, multiple sites of neovascularization were seen in several animals.The functional data correlated well with the morphological results: ERG signals were reduced in Crb2 KO mice already at the age of 1 month under both scotopic and photopic conditions, indicating alterations of both rod and cone system components, and decreased further with increasing age.

Conclusions: : The lack of CRB2 protein resulted in initial retinal layer defects and subsequently a progressive retinal degeneration, demonstrated functionally with electroretinography (ERG) and morphologically with SLO / OCT imaging.

Keywords: electroretinography: non-clinical • imaging/image analysis: non-clinical • retina