Retinal degeneration, a common culprit of vision loss, is often exacerbated by inflammation. Current treatments aimed at attenuating inflammation are not always effective, highlighting the need for alternative therapeutic targets to improve patient outcomes.
In this study, we employed RNA sequencing to uncover transcription factors involved in the inflammatory response, revealing that CCAAT enhancer binding proteins (CEBPs) play a central role in retinal degeneration-associated inflammation. Using siRNAs packaged in Invivofectamine and delivered intravitreally, we effectively inhibited CEBPs, leading to a substantial reduction in the inflammatory response, less loss of photoreceptor cells, and decreased levels of proinflammatory cytokines (Ccl2, Il6, Cxcl10) in the retina.
Moreover, employing single-cell RNA sequencing and RNAscope in situ hybridisation, we confirmed that CEBPs are predominantly expressed in glial cells and stressed photoreceptors. In vitro experiments also demonstrated that CEBPs translocate to the nucleus in response to proinflammatory stimuli.
In addition, our study demonstrated that chemical inhibitors of CEBPs effectively prevented retinal degeneration. These findings provide compelling evidence for CEBPs as ideal therapeutic targets in treating retinal degeneration.
To summarize, our investigation identifies CEBPs as pivotal modulators of the inflammatory response in the retina and underscores their therapeutic potential in mitigating retinal degeneration. Our results could help catalyze the development of more efficacious treatments for this incapacitating affliction.