Abstract
Purpose: :
The lens expresses AQP1 in its epithelium and AQP0 in its fiber cells. This study tests the hypothesis that AQP0 has some special role that cannot be fulfilled by AQP1.
Methods: :
A transgenic mouse that expressed AQP1 in lens fiber cells (AQP1-Tg) was constructed and crossed with AQP0 null (AQP-/-) mice to make a lens that expressed only AQP1 in epithelial and fiber cells. The rates of osmotically induced volume changes of fiber cell membrane vesicles were used to compare water transport in wild type (WT), AQP0-/-, AQP1-Tg and AQP1-Tg AQP0-/- mice.
Results: :
In WT mice, fiber cell membrane water permeability was 36±9 µm/s, which was increased by 2- to 3-fold by increases in intracellular calcium or extracellular hydrogen. Neither calcium nor pH affected the water permeability of AQP1. WT lenses had an average radius of 2.1±0.1 mm. AQP0-/- lenses had a 5-fold lower fiber cell membrane water permeability, significantly reduced lens size (radius of 1.7±0.1 mm), and a severe cataract. The AQP1-Tg fiber cell membrane water permeability was 123±35 µm/s. These lenses were transparent and the same size as WT. The AQP1-Tg AQP-/- fiber cell membrane water permeability was 95±11 µm/s, or 2.6-fold greater than that of WT. The lenses had a radius of 1.9±0.1 mm, somewhat smaller than WT but larger than AQP0-/-, and had mild central cataracts.
Conclusions: :
These results suggest water permeability is an important function of AQP0, but not its only function. Up regulation of AQP0 water permeability by intracellular calcium and external pH may represent one important role of AQP0 in the WT lens. However, fiber cells from AQP1-Tg AQP0-/- lenses had higher water permeability than those of WT lenses, yet the AQP1-Tg AQP0-/- lenses had mild central cataracts. In fiber cells, AQP0 forms square array junctions whereas AQP1 does not, so these junctions may be the special role of AQP0.
Keywords: transgenics/knock-outs • cell adhesions/cell junctions • cell membrane/membrane specializations