Nanophthalmos-Associated MYRF gene mutation facilitates intraocular inflammation in mice.

• A Myrf mutant mouse strain was generated to systemically investigate the role of Myrf in mice eyes. • Inflammation associated signaling pathways were enriched in Myrf mut/+ mice ocular tissues using RNA-Sequence. • After intravitreally injected with LPS, the inflammatory responses in Myrf mut/+ mice were more serious than that in Myrf +/+ mice and the inflammatory injury was ameliorated with DEX pretreatment. Patients with nanophthalmos might be prone to developing intraocular inflammation following an acute glaucoma attack. Here, we aimed to investigate the role of MYRF in intraocular inflammation by modeling the mutation in mice. Nanophthalmos frameshift mutation of Myrf was introduced into the mouse genome with the CRISPR-Cas9 system. Signaling pathways in eye tissues were delineated using RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Intraocular inflammation was induced by a lipopolysaccharide (LPS) intravitreal injection. Dexamethasone (DEX) was administered systemically and locally a week before the LPS injection. The anterior segment clinical scores of the mice were examined 24 h after the LPS injection. Infiltrating inflammatory cells were evaluated with histopathology and immunofluorescence. The mRNA levels of inflammatory cytokines were quantified with reverse transcription-quantitative PCR (RT-qPCR) and the corresponding protein concentrations using enzyme-linked immunosorbent assay (ELISA). Many inflammation-associated signaling pathways were enriched in Myrf mut/+ mice ocular tissues. Clinical scores of Myrf mut/+ mice were significantly higher than those of Myrf +/+ mice 24 h after LPS administration. Histological examination demonstrated high inflammatory cell infiltration in the anterior and vitreous chambers in Myrf mut/+ mice, with numerous CD45+ and CD11b+ inflammatory cells. Moreover, enhanced expression of inflammatory cytokines MCP-1, TGF-β, and IL-1β in eyes and aqueous humor of Myrf mut/+ mice was detected. Remarkably, pretreating Myrf mut/+ mice with DEX relieved the intraocular inflammation. Nanophthalmos-associated MYRF mutation renders mouse eyes more susceptible to inflammation. Dexamethasone treatment ameliorates the inflammatory response. [ABSTRACT FROM AUTHOR]