Retina-specific long non-coding RNAs associated with inherited retinal disease genes

Long non‑coding RNAs (lncRNAs) are increasingly recognized as important regulatory molecules, yet their roles remain largely unexplored in many tissues. This study aimed to identify and characterize lncRNAs involved in human retinal biology and inherited retinal disease (IRD), a leading cause of blindness worldwide. By integrating retinal tissue-specificity, location in IRD gene topologically associating domains (TADs), and co-expression analyses, we identified a set of 126 lncRNAs that are potentially regulating IRD genes. In-depth characterization of eleven selected lncRNAs, one of which is novel (LINC03128), allowed us to dissect their transcriptional units and cell type-specific expression, and revealed significant associations with visual function. Furthermore, knockdown of LINC03127 in human retinal explants and retinal organoids resulted in marked downregulation of photoreceptor-related gene pathways and pointed to a potential regulatory interaction with ABCA4, a major IRD gene located in cis. Collectively, our study provides the first systematic assessment of lncRNAs in the human retina and establishes a comprehensive resource of candidate regulatory lncRNAs with potential relevance to retinal function and disease.