Physiological Mechanisms Regulating Lens Transport

Abstract

The transparency and refractive properties of the lens are maintained by the cellular physiology provided by an internal microcirculation system that utilizes spatial differences in ion channels, transporters and gap junctions to establish standing electrochemical and hydrostatic pressure gradients that drive the transport of ions, water and nutrients through this avascular tissue. Aging has negative effects on lens transport, degrading ion and water homeostasis, and producing changes in lens water content. This alters the properties of the lens, causing changes in optical quality and accommodative amplitude that initially result in presbyopia in middle age and ultimately manifest as cataract in the elderly. Recent advances have highlighted that the lens hydrostatic pressure gradient responds to tension transmitted to the lens through the Zonules of Zinn through a mechanism utilizing mechanosensitive channels, multiple sodium transporters respond to changes in hydrostatic pressure to restore equilibrium, and that connexin hemichannels and diverse intracellular signaling cascades play a critical role in these responses. The mechanistic insight gained from these studies has advanced our understanding of lens transport and how it responds and adapts to different inputs both from within the lens, and from surrounding ocular structures.

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

“…Sensitive methods of light scattering in vivo can be correlated with recent MRI data from the systematic study of lens hydration. This can provide new insights into the functional relationship between transparency and microcirculation during development and aging (270,277).…”

“…Biochemically, the establishment and maintenance of symmetry to lens function is linked to the differential effects of growth factors and channel protein expression during development of the microcirculation system in the lens (29,45,262,270,277,299,(308)(309)(310)(311). While the importance of nutrition in lens transparency is also well known, the uniform spatial organization of fluid flow and its role in lens symmetry receives little attention (166,300,(312)(313)(314).…”

Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis

“…The loss of the antagonism of PI3K signaling in single PTEN KO lenses increased the activation of Akt, and reduced Na + /K + -ATPase activity within the epithelial cells [ 14 ]. This caused a reduction in the normal sodium and water efflux mediated by the lens circulation [ 48 , 49 ], resulting in an increased intracellular hydrostatic pressure and ultimately lens rupture. The single PTEN lens KO phenotype initially displayed the formation of a ring of densely packed cortical vacuoles in neonatal mice that could be eliminated by in utero treatment with an Akt inhibitor [ 14 ].…”

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

“…In the absence of blood vessels, survival of the fiber cells depends on an internal circulation system that allows delivery of ions and nutrients, and removal of waste metabolites to and from the center of the lens, respectively ( Mathias et al, 2007 ; Berthoud et al, 2020 ). Lens circulation depends on communication through intercellular gap junction channels ( Dawes et al, 2014 ; Berthoud and Ngezahayo, 2017 ; Berthoud et al, 2020 ; Giannone et al, 2021 ). Since Cx46 seems to be the most important connexin in fiber lens cells, its properties define the intracellular circuit properties in the lens ( Mathias et al, 2007 ; Berthoud et al, 2020 ).…”

“…The lens cells are subjected to a hard metabolic environment as they live under hypoxic conditions and do not have organelles. Cell-to-cell communication allows for the metabolic cooperation between lens cells through the fluxes of inorganic ions, small organic molecules and water ( Goodenough et al, 1980 ; Mathias et al, 1997 ; Harris and Locke, 2009 ; Valiunas et al, 2018 ), with the lens operating as a syncytium of cells interconnected by gap junction channels formed by proteins called connexins ( Goodenough, 1992 ; Giannone et al, 2021 ).…”