Abstract
Purpose :
Gene activity within the retina is highly regulated, particularly in photoreceptor cells where genetic dysregulation can lead to irreversible neuronal cell death, resulting in vision loss. PR/SET Domain 13 (PRDM13) is a transcriptional repressor important for defining excitatory neural lineages in the dorsal neural tube through regulation of basic helix-loop-helix (bHLH) genes. In the mature retina, PRDM13 is largely silent outside of some subtypes of amacrine cells; however, we have shown that overexpression of PRDM13 in the mature mammalian retina, for as little as 24 hours, leads to retinal dysfunction. Thus, we hypothesize that PRDM13 is able to regulate the expression of genes important for cell identity and survival of photoreceptors in the mammalian retina.
Methods :
To identify gene regulatory targets of PRDM13, we induced human PRDM13 overexpression for 72 hours in our adult mouse model. Neural retinas and RPE/eyecups were then collected and used in a bulk RNA sequencing experiment to identify differentially expressed genes following PRDM13 overexpression compared to controls.
Results :
Pathway analysis of the bulk RNA sequencing data between mice overexpressing PRDM13 and wildtype littermates revealed that genes important for gap junction-mediated intracellular transport, negative regulation of neurogenesis, and visual system development – including bHLH genes – were significantly impacted by PRDM13 overexpression.
Conclusions :
Our data suggests that PRDM13 maintains its role as a transcriptional repressor in the mature retina, with the majority of differentially expressed genes being downregulated compared to control retinas. Additionally, we see that PRDM13 overexpression leads to differential expression of some, but not all, bHLH genes in the mature retina. Our data also suggests novel functions of PRDM13 as a transcriptional regulator for genes involved in proper retinal function, such as gap junction intracellular transport. Further investigation into the regulatory role of PRDM13 in the adult mammalian retina will elucidate novel genes and pathways which are important for retinal health and function.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.