Identification and application of p75 neurotrophin receptor-expressing human trabecular meshwork progenitor cells

Abstract

The trabecular meshwork (TM) is a tissue that originates from the neural crest via the periocular mesenchyme and plays a role in draining water and maintaining intraocular pressure (IOP). Damage to the TM is associated with pathologically elevated IOP, and cell-based therapy is expected to restore the functions of the TM in the future. Here, we aimed to isolate and characterize TM progenitor cells (TMPs) from human TM tissues. We focused on the p75 neurotrophin receptor (p75), a stem cell marker of the neural crest. Approximately 32% of p75-expressing cells were present in the TM. P75-expressing TMPs could proliferate in serum-free culture. The colony formation efficiency of TMPs was 1.11 ± 0.18%. TMPs showed a markedly lower proliferation ability for passaging. TMPs expressed neural crest markers (p75, Sry-box [SOX] 9, SOX10, transcription factor AP [TFAP] 2B); nestin; periocular mesenchymal markers (Forkhead box [FOX] C1, FOXC2, and paired-like homeodomain transcription factor 2); and CD166, but not TM differentiation markers. The TMPs differentiated into mature TM cells (dTMCs) and keratocytes. dTMCs from TMPs expressed high levels of TM markers (aquaporin 1, matrix gla protein, prostaglandin D2 synthase, and AnkG). Furthermore, the TMPs showed enhanced expression of myocilin, a glaucoma susceptibility gene, following induction of differentiation by dexamethasone. TMPs also differentiated into adipocytes, osteocytes, and chondrocytes. These data suggest that p75-expressing TMPs could be a useful cell source in cell-based therapy and pathological models of glaucoma.