Crb1, short for Crumbs homolog 1, is a gene that plays a crucial role in the retina. Its normal expression is enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, and it is involved in maintaining the integrity of the outer blood-retinal barrier and colonic intestinal epithelial barrier. Mutations in Crb1 are associated with various retinal degenerations, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) [1].

In murine models with the Rd8 mutation of Crb1, there is intralesional bacteria in the retinas. The mutation dampens Crb1 expression at both the retinal and colonic sites, leading to the impairment of the outer blood-retinal barrier and colonic intestinal epithelial barrier. This results in the translocation of intestinal bacteria from the lower gastrointestinal tract to the retina, causing secondary retinal degeneration. Depleting bacteria systemically or re-introducing normal Crb1 expression colonically can rescue Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach [1]. In human induced pluripotent stem cell-derived retinal organoids of patients with retinitis pigmentosa caused by biallelic Crb1 mutations, there are decreased levels of Crb1 and NOTCH1 expression at the retinal outer limiting membrane, along with changes in endosome-related components, highlighting the importance of Crb1 in early endosome maturation receptor recycling in the retina [2].

In conclusion, Crb1 is essential for maintaining the integrity of barriers in the retina and colon, and its normal function is crucial for preventing retinal degeneration. Mouse models with Crb1 mutations, like the Rd8-mutated mice, have revealed the pathogenic mechanism of Crb1-mutation-associated retinal degenerations, providing insights into potential treatments such as the use of antimicrobial agents for these blinding diseases [1].

References:

1. Peng, Shanzhen, Li, Jing Jing, Song, Wanying, Zhang, Feng, Wei, Lai. 2024. CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut. In Cell, 187, 1387-1401.e13. doi:10.1016/j.cell.2024.01.040. https://pubmed.ncbi.nlm.nih.gov/38412859/

2. Buck, Thilo M, Quinn, Peter M J, Pellissier, Lucie P, Jost, Carolina R, Wijnholds, Jan. 2023. CRB1 is required for recycling by RAB11A+ vesicles in human retinal organoids. In Stem cell reports, 18, 1793-1810. doi:10.1016/j.stemcr.2023.07.001. https://pubmed.ncbi.nlm.nih.gov/37541258/