The trabecular meshwork (TM) of the eye is critical in maintaining aqueous humor outflow and intraocular pressure (IOP). The cellular density in the TM decreases with age and is particularly low in eyes with glaucoma. TM cells are thought to be derived from a population of stem cells, referred to as TM stem cells (TMSCs). To investigate the relationship between TM cellular density and TMSCs, the number of TMSCs and TM cells was compared in human eyes obtained from young donors, individuals with glaucoma, and age-matched controls. Findings obtained confirm that eyes of younger donors contain the largest number of TM cells, while those of older healthy donors contained more TM cells than glaucomatous eyes of the same age (p=0.0007). Likewise, we detected the largest number of TMSCs in young eyes, significantly higher than in healthy older eyes (p<
0.0001). Again, eyes from glaucomatous patients contained fewer TMSC than those of healthy donors (p<
0.0001). Together the data indicate a clear decline in the number of TMSCs with age and a further reduction in eyes with glaucoma. Although this study does not establish causality, our finding is consistent with the notion that the degeneration or loss of stemness of TMSCs is the cause of reduced TM cellularity which, in turn, is associated with TM dysfunction and the development of elevated IOP.