Active Maintenance of the Gradient of Refractive Index Is Required to Sustain the Optical Properties of the Lens

Vaghefi, Ehsan; Kim, Andy; Donaldson, Paul J.

doi:10.1167/iovs.15-17861

Cited by 43 publications

(62 citation statements)

References 52 publications

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“…We have previously shown that Cx46fs380 distorts lens focusing, suggesting altered lens refraction (28). In cultured bovine lenses, inhibition of the lens circulation also alters the gradient of refractive index and lens optical properties (39). The gradient of refractive index in the lens depends on the radial gradient of protein concentration (33), which may relate to the lens intracellular hydrostatic pressure (15).…”

Section: Discussionmentioning

confidence: 99%

Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice

Gao

Minogue

Beyer

et al. 2018

American Journal of Physiology-Cell Physiology

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The lens is an avascular organ whose function and survival depend on an internal circulation system. Cx46fs380 mice model a human autosomal dominant cataract caused by a mutant lens connexin. In these mice, fiber cell connexin levels and gap junction coupling are severely decreased. The present studies were conducted to examine components of the lens circulation system that might be altered and contribute to the pathogenesis of cataracts. Lenses from wild-type mice and Cx46fs380 heterozygotes and homozygotes were studied at 2 months of age. Cx46fs380-expressing lens fiber cells were depolarized. Cx46fs380 lenses had increased intracellular hydrostatic pressure and concentrations of Na and Ca. The activity of epithelial Na-K-ATPase was decreased in Cx46fs380 lenses. All of these changes were more severe in homozygous than in heterozygous Cx46fs380 lenses. Cx46fs380 cataracts were stained by Alizarin red, a dye used to detect insoluble Ca. These data suggest that the lens internal circulation was disrupted by expression of Cx46fs380, leading to several consequences including accumulation of Ca to levels so high that precipitates formed. Similar Ca-containing precipitates may contribute to cataract formation due to other genetic or acquired etiologies.

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Section: Discussionmentioning

confidence: 99%

Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice

Gao

Minogue

Beyer

et al. 2018

American Journal of Physiology-Cell Physiology

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“…The pressure gradient has a parabolic form reminiscent of the GRIN and indeed it has been suggested that the bulk flow of water may play a role in establishing the index gradient (Gao et al, 2013, 2015). In support of an active role for the lens microcirculation in generating and maintaining the GRIN, MRI imaging has been used to demonstrate that in the presence of high potassium solutions, low temperature, or ouabain (an inhibitor of the Na/K-ATPase), the water-protein gradient of the lens collapses and negative spherical aberration is reduced leading to reduced image quality (Vaghefi et al, 2011, 2015). On the basis of these findings it was concluded that the protein concentration gradients that underlie the GRIN are actively maintained through membrane-based processes.…”

Section: Mechanism Of Compactionmentioning

confidence: 99%

The cause and consequence of fiber cell compaction in the vertebrate lens

Bassnett

Costello²

2017

Experimental Eye Research

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Fiber cells of the ocular lens are arranged in a series of concentric shells. New growth shells are added continuously to the lens surface and, as a consequence, the preexisting shells are buried. To focus light, the refractive index of the lens cytoplasm must exceed that of the surrounding aqueous and vitreous humors, and to that end, lens cells synthesize high concentrations of soluble proteins, the crystallins. To correct for spherical aberration, it is necessary that the crystallin concentration varies from shell-to-shell, such that cellular protein content is greatest in the center of the lens. The radial variation in protein content underlies the critical gradient index (GRIN) structure of the lens. Only the outermost shells of lens fibers contain the cellular machinery necessary for protein synthesis. It is likely, therefore, that the GRIN (which spans the synthetically inactive, organelle-free zone of the lens) does not result from increased levels of protein synthesis in the core of the lens but is instead generated through loss of volume by inner fiber cells. Because volume is lost primarily in the form of cell water, the residual proteins in the central lens fibers can be concentrated to levels of >500 mg/ml. In this short review, we describe the process of fiber cell compaction, its relationship to lens growth and GRIN formation, and offer some thoughts on the likely nature of the underlying mechanism.

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“…They are robust to variations of intracellular pressure. The evolutionary advantage of this adaptation is not clear to us, but may be more obvious to other workers with a greater knowledge of clinical realities that show how the lens becomes diseased [63,46,48,49]. Our simplified model suggests that all the quantities can be computed without knowing the intracellular pressure.…”

Section: Introductionmentioning

confidence: 99%

A Bidomain Model for Lens Microcirculation

Zhu

Eisenberg

et al. 2019

Biophysical Journal

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There exists a large body of research on the lens of mammalian eye over the past several decades. The objective of the current work is to provide a link between the most recent computational models and some of the pioneering work in the 1970s and 80s. We introduce a general non-electro-neutral model to study the microcirculation in lens of eyes. It describes the steady state relationships among ion fluxes, water flow and electric field inside cells, and in the narrow extracellular spaces between cells in the lens. Using asymptotic analysis, we derive a simplified model based on physiological data and compare our results with those in the literature. We show that our simplified model can be reduced further to the first generation models while our full model is consistent with the most recent computational models. In addition, our simplified model captures the main features of the full model. Our results serve as a useful link intermediate between the computational models and the first generation analytical models. Simplified models of this sort may be particularly helpful as the roles of similar osmotic pumps of microcirculation are examined in other tissues with narrow extracellular spaces, like cardiac and skeletal muscle, liver, kidney, epithelia in general, and the narrow extracellular spaces of the central nervous system, the "brain". Simplified models may reveal the general functional plan of these systems before full computational models become feasible and specific. convection to bring materials close enough to cells so diffusion to and across cell membranes can provide what the cell needs to live.The circulatory system of blood vessels-arteries, veins, and capillaries-provides the convection in almost all tissues. But there is one clear exception, the lens of the (mammalian) eye. The lens does not have blood vessels, presumably because even capillaries would so seriously interfere with transparency. The lens is large, much larger than the length scale on which diffusion itself is efficient. The lens must provide nutrients through another kind of convection, a microcirculation of water that moves nutrients into the lens and rinses wastes out of it. The microcirculation is in fact driven by the lens itself, without an external 'pump'. The lens is itself an osmotic pump.The lens is an asymmetrical electrical syncytium in which all cells are electrically coupled one to another, with a narrow extracellular space between the cells (see Fig.1). The extracellular space is filled with ionic solution in free diffusion with the plasma outside cells. It may also contain specialized more or less immobile proteins and specialized polysaccharides, as well as containing obstructions formed by the connexin proteins themselves. The intracellular space behaves very much as a large single cell would, with the bio-ions of classical electro-physiology (Na + , K + , Cl − ) free to move without much resistance from cell to cell, and many solutes of significant size (say with diameter less than 1.5 nm) able to move as well. The i...

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Active Maintenance of the Gradient of Refractive Index Is Required to Sustain the Optical Properties of the Lens

Cited by 43 publications

References 52 publications

Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice

Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice

The cause and consequence of fiber cell compaction in the vertebrate lens

A Bidomain Model for Lens Microcirculation

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