Top2b-Regulated Genes and Pathways Linked to Retinal Homeostasis and Degeneration

Retinal homeostasis and degeneration are significant contributors to global vision loss, with retinal health primarily assessed by the count and function of photoreceptor cells, the most abundant cells in the retina. Genomic studies have identified topoisomerase II beta (Top2b), an enzyme that untangles DNA supercoils to facilitate gene expression, as a critical transcriptional regulator for retinal health. This review aims to uncover and categorize genes linked to Top2b that are dynamically expressed during retinal degeneration, revealing shared and overlooked regulatory pathways. RNA sequencing data from wild-type and Top2b knockout mice revealed thousands of differentially expressed genes regulated by Top2b. By cross-referencing these genes with retinal degeneration datasets, including RetNet and the Gene Ontology Browser, we identified 44 Top2b-linked genes associated with retinal degeneration. These genes were grouped into fourteen functional categories: ciliary function and trafficking, metabolism, synaptic transmission, transcription factors and regulation, visual cycle, retinoids, and more. Key genes such as Bbs7, Ubb, Rbp4, Cetn2, Pik3r1, and Crx were explored, and their critical pathways for retinal health were outlined. This comprehensive catalog of 44 Top2b-linked retinal homeostatic genes will serve as a valuable resource for researchers. It provides new insights into the regulatory mechanisms underlying retinal homeostasis, setting the framework for the development of targeted therapeutic approaches and early intervention strategies for preventing photoreceptor loss.