Angiogenesis may pose a clinical challenge in glaucoma, for example during the wound healing phase after glaucoma filtration surgery and in a severe form of secondary glaucoma called neovascular glaucoma (NVG). Up regulation of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, occurs in eyes that have undergone glaucoma filtration surgery, as well as those with NVG. This has led to studies investigating the ability of anti-VEGF therapy to improve outcomes, and we examine their findings with respect to the safety and efficacy of anti-VEGF agents, mainly bevacizumab and ranibizumab, in eyes that have undergone glaucoma filtration surgery or have NVG. Combining conventional therapies—such as anti-metabolites after filtration surgery and panretinal photocoagulation in NVG—and anti-VEGF drugs may achieve a synergetic effect, although further studies are required to evaluate the long-term efficacy of combination treatments.

SUMMARY Stem cell niches provide a microenvironment to support the self-renewal and multi-lineage differentiation of stem cells. Cell-cell interactions within the niche are essential for maintaining tissue homeostasis. However, the niche cells supporting mesenchymal stem cells (MSCs) are largely unknown. Using single-cell RNA sequencing, we show heterogeneity among Gli1+ MSCs and identify a subpopulation of Runx2+/Gli1+ cells in the adult mouse incisor. These Runx2+/Gli1+ cells are strategically located between MSCs and transit-amplifying cells (TACs). They are not stem cells but help to maintain the MSC niche via IGF signaling to regulate TAC proliferation, differentiation, and incisor growth rate. ATAC-seq and chromatin immunoprecipitation reveal that Runx2 directly binds to Igfbp3 in niche cells. This Runx2-mediated IGF signaling is crucial for regulating the MSC niche and maintaining tissue homeostasis to support continuous growth of the adult mouse incisor, providing a model for analysis of the molecular regulation of the MSC niche.

No abstract