New study shows requirement of Rab28 in outer segment phagocytosis
Since linkage of human RAB28 mutations to inherited blindness and cone-rod dystrophy, studies have focused on Rab28 function in the retina. However, there remains a vast gap in understanding of the protein networks regulated by Rab28. Researchers from, among others, the zebrafish facility endeavored to bridge that void, to shed more light on Rab28 function and Rab28-CRD disease mechanisms. Thie study uncovered that Rab28 is required from the larval zebrafish stage for the burst of RPE phagocytosis, of the photoreceptor outer segments at both dawn and dusk peaks. They further investigated the regulation of OSP in the zebrafish model and the role of Rab28. Using a gene complementation approach, it was found that Rab28 plays an important role in the cone photoreceptors, as cone-specific expression of Rab28 was sufficient to restore the OSP defect in the knockout model. Proteomic analysis by mass spectrometry demonstrates loss of Rab28 effects the expression profile of several known regulators of OSP and identified potential novel regulators of the OSP process. rab28 KO can result in long-term physiological effects on the retina, as retinoid and bisretinoid analysis on therab28 KO revealed altered levels of visual cycle components, as well as an increase in the toxic vitamin A compound A2PE.