Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells’ response to Pten deletion

• DOI: 10.1073/pnas.2113751119
• Publication Date: 2022-04-08T18:14:36Z
• Authors: Lili Xie; Ling-Ping Cen; Yiqing Li; Hui-Ya Gilbert; Oleksandr Strelko; Cynthia Berlinicke; Mihaela A. Stavar...; Madeline Ma; Yongting Wang; Qi Cui; Michael G. Kaplitt; Donald J. Zack; Larry I. Benowitz; Yuqin Yin
• Keywords: Tensin

Although mammalian retinal ganglion cells (RGCs) normally cannot regenerate axons nor survive after optic nerve injury, this failure is partially reversed by inducing sterile inflammation in the eye. Infiltrative myeloid express axogenic protein oncomodulin (Ocm) but additional, as-yet-unidentified, factors are also required. We show here that infiltrative macrophages stromal cell–derived factor 1 (SDF1, CXCL12), which plays a central role regard. Among many growth tested culture, only SDF1 enhances Ocm activity, an effect mediated through intracellular cyclic AMP (cAMP) elevation and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation. deficiency (CXCL12flx/flxLysM-Cre−/+ mice) or deletion of receptor CXCR4 RGCs (intraocular AAV2-Cre CXCR4flx/flx antagonist AMD3100 greatly suppresses inflammation-induced regeneration decreases RGC survival to baseline levels. Conversely, induces survival, and, when combined with Ocm/cAMP, increases axon levels similar those induced intraocular inflammation. In contrast phosphatase tensin homolog (Pten), promotes selectively from αRGCs, non-αRGCs enables latter respond robustly Pten deletion; however, surprisingly diminishes response αRGCs deletion. When deletion, entire length nerve. Thus, complements effects mediating different subtypes