Systemic whole transcriptome analysis identified underlying molecular characteristics and regulatory networks implicated in the retina following optic nerve injury

Abstract

Optic nerve injuries are severely disrupt the structural and functional integrity of the retina, often leading to visual impairment or blindness. Despite the profound impact of these injuries, the molecular mechanisms involved remain poorly understood. In this study, we performed a comprehensive whole-transcriptome analysis of mouse retina samples after optic nerve crush (ONC) to elucidate changes in gene expression and regulatory networks. Transcriptome analysis revealed a variety of molecular alterations, including 256 mRNAs, 530 lncRNAs, and 37 miRNAs, associated with metabolic, inflammatory, signaling, and biosynthetic pathways in the injured retina. The integrated analysis of co-expression and protein-protein interactions identified an active interconnected module comprising 5 co-expressed proteins (Fga, Serpina1a, Hpd, Slc38a4, and Ahsg) associated with the complement and coagulation cascades. Finally, 2 mRNAs (Slc38a4 and Fga), 2 miRNAs (miR-671-5p and miR-3057-5p), and 6 lncRNAs (MSTRG.1830.1, Gm10814, A530013C23Rik, Gm40634, MSTRG.9514.1, A330023F24Rik) were identified by qPCR in 661W and HEK293T cells, and some of them were validated as critical components of a ceRNA network active in the injured retina through dual-luciferase reporter assays. In conclusion, our study provides comprehensive insight into the complex and dynamic biological mechanisms involved in retinal injury responses and highlights promising potential targets to enhance neuroprotection and restore vision.