Variants in the protein RAB28 can cause autosomal recessive cone-rod dystrophy (CRD) a type of human inherited blindness. When a condition is inherited in an autosomal recessive manner, it means that both copies of the associated gene don’t work properly, giving rise to the condition. In this case, the individual’s mother and father have both passed on a mutation, or a DNA change, for the gene in question.
This collaborative project used small tropical zebrafish as a research model. Despite their underwater habitat, the zebrafish have eyes and genes similar to humans, making them an excellent model for ocular research. Previous studies have shown that both in humans and zebrafish, Rab28 is important for having normal levels of outer segment phagocytosis (OSP), an essential process for waste removal and recycling within the eye.
Waste removal and recycling is necessary for the light-sensing photoreceptors in the eye to stay healthy, and one way this is achieved is by cells adjacent to the photoreceptors “pruning” their tips, a process called outer segment phagocytosis(OSP). Mutations in genes that control OSP are known to be linked to inherited retinal disease, so it is important we understand their roles in the OSP process.
This study sheds light into the molecular mechanisms by which Rab28 controls OSP and inherited blindness and provides greater understanding into RAB28-associated CRD. Moreover, a future perspective of this study would be the use of RAB28 for gene-therapy approaches.