Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells

Abstract

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (P) some 20 times higher than AQP0, AQP5 could function to modulate P in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative P of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of P, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg-sensitive contribution to P. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg-sensitive P was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating P in the outer cortex.

Changes to zonular tension alters the subcellular distribution of AQP5 in regions of influx and efflux of water in the rat lens

“…Interestingly, this removal of AQP5 from the membrane is only transient in lenses organ cultured without their zonules attached ( Figure 3B). In an earlier study, we showed a similar increase in AQP5 membrane labelling in the equatorial efflux zone and, in addition, showed that this increase in membrane labelling was associated with an increase in the Hg + -sensitive PH2O measured in fiber membrane vesicles derived from organ cultured rat lenses 27 . This earlier study indicates that the changes in the subcellular location of AQP5 labelling observed using immunohistochemistry in the current study are associated with changes in PH2O and support the suggestion that AQP5 functions as a regulated water channel in the anterior influx and equatorial efflux zones of the rat lens.…”

“…AQP5, in other tissues, has been shown to act as a regulated water channel with a relatively high PH2O, which when inserted into the membrane increases the PH2O of epithelial cells [23][24][25][26] . In the lens, immunohistochemical mapping of the subcellular distribution of AQP5 has shown it to be expressed in both the epithelium and throughout the fiber cell mass 22,27 . In peripheral fiber cells it is initially found as a cytoplasmic pool of protein that undergoes a transition to the membrane as fiber cells differentiate and become internalized.…”

The Role of Aquaporins in Ocular Lens Homeostasis

“…Immunolabeling of lens sections has shown that AQP5 in peripheral fiber cells is predominantly cytoplasmic before transitioning to the plasma membrane in deeper lying fiber cells. In addition to this differentiation-dependent insertion of AQP5 into the membrane, Petrova et al have recently observed a dynamic insertion of AQP5 into the membrane of peripheral fiber cells in lenses that have been first subjected to organ culture [ 101 ]. In this study, they also showed that this insertion of AQP5 was correlated with a significant increase in a Hg 2+ -sensitive contribution to P H2O .…”

“…Thus, it is interesting to speculate that TRPV1/4 channel activation in response to changes in hydrostatic pressure may provide a link between changes in Na + /K + ATPase activity, the modulation of water permeability in peripheral fiber cells, and the dynamic maintenance of the optical properties of the lens. Thus it would appear that the observed dynamic insertion of AQP5 into the membrane of DF cells in response to lens organ culture [ 101 ] may be in response to changes in the hydrostatic pressure gradient that are sensed by TRP channels that, in turn, activate signaling pathways that alter both ion transport and water permeability in parallel to ensure the optical properties of the lens remain constant.…”

A comprehensive review of available omics data resources and molecular profiling for precision glioma studies (Review)

“…A number of studies have demonstrated that the methylation state of the MGMT gene is closely associated with the response to temozolomide (41). Specifically, if the promoter is methylated, the treatment is more effective; otherwise, the patient is not sensitive, suggesting that MGMT promoter methylation is a favorable predictor for overall survival and progression-free survival in glioma (42,43). At present, MGMT has also been revealed to be a useful tool for increasing gene therapy efficiency, and with applications in clinical detection (44).…”