Journal
SCIENCE ADVANCES
Volume 8, Issue 7, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abj4833
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Funding
- NIH [P41-GM103540, P50-GM076516, R01-EY05661, R01-EY031587]
- Balsells Fellowship from the Generalitat de Catalunya
- PEDECIBA
- Agencia Nacional de Investigacion e Innovacion (ANII) grant [FCE_3_ 2018_1_149047]
- FOCEM (Fondo para la Convergencia Estructural del Mercosur) [COF 03/11]
- Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation [2020-225439]
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Macromolecular crowding and water dynamics play important roles in cellular homeostasis and fate determination. Understanding macromolecular crowding in the lens is crucial for preventing eye diseases such as cataract and presbyopia. This study combines the use of a nanoenvironmental sensor and zebrafish mutants to investigate the spatial regulation of macromolecular crowding and the roles of specific aquaporin proteins in the lens.
Macromolecular crowding is crucial for cellular homeostasis. In vivo studies of macromolecular crowding and water dynamics are needed to understand their roles in cellular physiology and fate determination. Macromolecular crowding in the lens is essential for normal optics, and an understanding of its regulation will help prevent cataract and presbyopia. Here, we combine the use of the nanoenvironmental sensor [6-acetyl-2-dimethylaminonaphthalene (ACDAN)] to visualize lens macromolecular crowding with in vivo studies of aquaporin 0 zebrafish mutants that disrupt its regulation. Spectral phasor analysis of ACDAN fluorescence reveals water dipolar relaxation and demonstrates that mutations in two zebrafish aquaporin 0s, Aqp0a and Aqp0b, alter water state and macromolecular crowding in living lenses. Our results provide in vivo evidence that Aqp0a promotes fluid influx in the deeper lens cortex, whereas Aqp0b facilitates fluid efflux. This evidence reveals previously unidentified spatial regulation of macromolecular crowding and spatially distinct roles for Aqp0 in the lens.
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