Upregulation of the PPAR signaling pathway and accumulation of lipids are related to the morphological and structural transformation of the dragon-eye goldfish eye

Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable
models for evolutionary developmental biology. The dragon-eye strain is characterized by protruding eyes (analogous to those of
Chinese dragons). Although the strain has been selected for about 400 years, the mechanism of its eye development remains
unclear. In this study, a stable dragon-eye goldfish strain with a clear genetic background was rapidly established and studied. We
found that upregulation of the PPAR signaling pathway accompanied by an increase in lipid accumulation might trigger the
morphological and structural transformation of the eye in dragon-eye goldfish. At the developmental stage of proptosis (eye
protrusion), downregulation of the phototransduction pathway was consistent with the structural defects and myopia of the
dragon-eye strain. With the impairment of retinal development, cytokine-induced inflammation was activated, especially after
proptosis, similar to the pathologic symptoms of many human ocular diseases. In addition, differentially expressed transcription
factors were significantly enriched in the PAX and homeobox families, two well-known transcription factor families involved in
eye development. Therefore, our findings reveal the dynamic changes in key pathways during eye development in dragon-eye
goldfish, and provide insights into the molecular mechanisms underlying drastically altered eyes in goldfish and human ocular
disease.