Lens Aquaporins in Health and Disease: Location is Everything!

Abstract

Cataract and presbyopia are the leading cause of vision loss and impaired vision, respectively, worldwide. Changes in lens biochemistry and physiology with age are responsible for vision impairment, yet the specific molecular changes that underpin such changes are not entirely understood. In order to preserve transparency over decades of life, the lens establishes and maintains a microcirculation system (MCS) that, through spatially localized ion pumps, induces circulation of water and nutrients into (influx) and metabolites out of (outflow and efflux) the lens. Aquaporins (AQPs) are predicted to play important roles in the establishment and maintenance of local and global water flow throughout the lens. This review discusses the structure and function of lens AQPs and, importantly, their spatial localization that is likely key to proper water flow through the MCS. Moreover, age-related changes are detailed and their predicted effects on the MCS are discussed leading to an updated MCS model. Lastly, the potential therapeutic targeting of AQPs for prevention or treatment of cataract and presbyopia is discussed.

Proteome Remodeling of the Eye Lens at 50 Years Identified With Data-Independent Acquisition

“…Previous publications have thoroughly reviewed the importance of AQPs in the lens MCS ( 12 , 21 , 56 , 57 , 58 , 59 ). Briefly, AQPs serve as water channels that facilitate water permeability in fiber cells ( 48 ).…”

Proteome Remodeling of the Eye Lens at 50 Years Identified with Data-Independent Acquisition

“…Previous publications have thoroughly reviewed the importance of aquaporins in the lens MCS (12, 27, 75–78). Briefly, aquaporins serve as water channels that facilitate water permeability in fiber cells.…”

Novel MIP gene mutation causes autosomal-dominant congenital cataract

“…We found that both wild-type and mutant PCS2+MIP lens fibres were uniformly transparent (Figure 12). DISCUSSION Aquaporins (AQPs) mainly mediate passive free water transfer across biofilms along the osmotic pressure gradient, thereby they play an important role in regulating lens water metabolism, maintaining lens internal microcirculation homeostasis, and participating in lens physiological functions and transparency [40][41] . AQPs are a superfamily of MIPs of approximately 30 kDa that are expressed in prokaryotes and eukaryotes, three of which are present in the mammalian lens (AQP0, AQP1, and AQP5) [42] .…”