The Effects of Glaucoma Drainage Devices on Oxygen Tension, Glycolytic Metabolites, and Metabolomics Profile of Aqueous Humor in the Rabbit.

PURPOSE: Glaucoma drainage device (GDD) implantation can lead to corneal decompensation. We evaluated changes over time in oxygen tension and in the metabolic environment of the aqueous humor after GDD implantation in the rabbit eye. METHODS: Ahmed Glaucoma Valves were implanted in the left eyes of eight male New Zealand white rabbits. Right eyes were used as a control. Oxygen tension was measured immediately before surgery and at 1 and 2 months postoperation. Aqueous humor was collected from the surgical and control eyes at 1, 2, and 5 months postoperation. Aqueous humor samples collected at 1 and 5 months postoperation were selected for broad-spectrum metabolomics analysis using ultra-performance liquid chromatography-time of flight-mass spectrometry (UPLC TOF-MS). Multivariate analysis methods were used to identify metabolite profiles that separated the surgical and control eye at 1 and 5 months. RESULTS: There was a significant decrease in oxygen tension in aqueous humor of the surgical eyes (9 mm Hg, 95% confidence interval [CI]: -14.7 to -3.5). Differences in the metabolic profiles between the surgical and control eye at 1 and 5 months were observed, as were differences for the surgical eye at 1 and 5 months. In addition, a metabolite profile was identified that differentiated the surgical eyes at 1 and 5 months. CONCLUSION: Changes in the oxygen tension and metabolic intermediates occur within the aqueous humor as early as 1 month after GDD implantation. TRANSLATIONAL RELEVANCE: Corneal decompensation following GDD implantation could be secondary to disruption of the normal aqueous circulation, resulting in hypoxia and an altered metabolic profile. Alterations to the GDD design might minimize aqueous disruption and prevent corneal decompensation.

Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1.

Multipotent stromal cells (MSCs) have been shown to reduce apoptosis in injured cells by secretion of paracrine factors, but these factors were not fully defined. We observed that coculture of MSCs with previously UV-irradiated fibroblasts reduced apoptosis of the irradiated cells, but fresh MSC conditioned medium was unable reproduce the effect. Comparative microarray analysis of MSCs grown in the presence or absence of UV-irradiated fibroblasts demonstrated that the MSCs were activated by the apoptotic cells to increase synthesis and secretion of stanniocalcin-1 (STC-1), a peptide hormone that modulates mineral metabolism and has pleiotrophic effects that have not been fully characterized. We showed that STC-1 was required but not sufficient for reduction of apoptosis of UV-irradiated fibroblasts. In contrast, we demonstrated that MSC-derived STC-1 was both required and sufficient for reduction of apoptosis of lung cancer epithelial cells made apoptotic by incubation at low pH in hypoxia. Our data demonstrate that STC-1 mediates the antiapoptotic effects of MSCs in two distinct models of apoptosis in vitro.