Abstract Retinal ganglion cell (RGC) loss involves p53 activation and calcium overload. The role of RNA-binding proteins like ELAVL1 in this process remains unclear. We investigated whether ELAVL1 protects retinal cells by post-transcriptionally regulating WD Repeat Domain 36 (WDR36). In vitro stress was modeled using oxygen-glucose deprivation/reperfusion (OGD/R) in R28 retinal precursor cells. In vivo acute intraocular pressure (IOP) elevation was induced in mice. We modulated gene expression with siRNA, plasmids, or AAV vectors, assessing cell death, calcium levels, and protein markers. OGD/R downregulated ELAVL1 and WDR36 protein, but not WDR36 mRNA. ELAVL1 bound WDR36 mRNA and promoted its protein translation. Overexpression of either ELAVL1 or WDR36 reduced OGD/R-induced cell death, calcium overload, and p53 pathway activation. Crucially, WDR36 knockdown abolished ELAVL1’s protective effects in vitro . In vivo , AAV-mediated ELAVL1 overexpression mitigated IOP-induced retinal damage and apoptosis, which was reversed by co-knockdown of WDR36. The ELAVL1-WDR36 axis is a critical post-transcriptional mechanism that promotes retinal cell survival under acute pressure-ischemia stress by inhibiting p53 activation and calcium overload, highlighting its therapeutic potential.
Meng et al. (Thu,) studied this question.