Neuro‐retinal disorders in Trf2 mutant zebrafish

Abstract

By applying ionizing irradiation (IR+) on wild‐type (WT), and Trf2 mutant (both homo and heterozygous mutant) backgrounds, we observed the neurodegenerative phenotypes and neuro‐retinal disorders in the adult zebrafish and their offspring. The offspring from irradiated parental fish revealed several malformations in eyes during early development, suggesting that the integrity of the gametogenic processes is compromised beyond generations. We have identified abnormal neuro‐retinal development in the homozygous Trf2 mutant embryos that also accelerated retinal aging symptoms in adult heterozygous Trf2 mutant fish. The partial loss‐of‐function (decrease‐of‐function) of telomeric protein TRF2 is responsible for late‐onset retinal disorders as well as neuro‐retinal development with losing genomic integrity. A functional link and crosstalk between p53 and TRF2 in neuro‐retinal development has been demonstrated in both embryonic neuro‐retinal development and adult retinal function in zebrafish. The genetic effects of TRF2 and p53 insufficiency in neuro‐retinal systems of IR+ adults and their offspring detected. In the adult Trf2 mutant fish, we observed the development of AMD (age‐related macular degenerative disease)‐like symptoms with retinal dysfunctions. In our preliminary results, adult heterozygous Trf2 mutant fish showed accumulations of autofluorescent drusen‐like material around the retinal pigment epithelium (RPE) in their earlier age than that of WT siblings. The age‐related macular degeneration caused by the accumulation of lipofuscin in RPE revealed in the retinae of Trf2 mutant zebrafish. These studies exposed a new insight into retinal disorders in Vertebrates and established zebrafish as an efficient model organism for studying human retinal abnormalities and stress‐associated neural disease researches.