Throughout life, lens epithelial cells at the equator divide and develop into lens fibers, resulting in continual growth of the lens (see Chapter 2, Figs 2-2 and 2-5, in this volume). The lens cells with the highest metabolic rate are found in the epithelium and outer cortex. These superficial cells utilize oxygen and glucose for the active transport of electrolytes, carbohydrates, and amino acids into the lens. Because the lens is avascular, the task of maintaining transparency poses several challenges. The older cells, found toward the center of the lens, must be able to communicate with the superficial cells and the environment outside the lens. This communication is accomplished through low-resistance gap junctions that facilitate the exchange of small molecules from cell to cell. Lens fiber cells also have abundant water channels in their membranes, made up of MIP. It is not yet certain whether MIP serves primarily in the lens as a water channel, as an adhesion molecule that minimizes the extracellular space between fiber cells, or as both. Minimizing the extracellular space between fiber cells is important in reducing the scattering of light as it passes through the lens.
Maintenance of Lens Water and Cation Balance
The normal human lens contains approximately 66% water and 33% protein, and this proportion changes very little with aging. The lens cortex is more hydrated than the lens nucleus. About 5% of the lens volume is the water found between the lens fibers in the extracellular spaces. Within the lens, sodium and potassium concentrations are maintained at 20 millimolar (mM) and 120 mM, respectively.
Perhaps the most important aspect of lens physiology is the mechanism that controls water and electrolyte balance, which is critical to lens transparency. Because transparency is highly dependent on the structural and macromolecular components of the lens, perturbation of cellular hydration can readily lead to opacification. It is noteworthy that disruption of water and electrolyte balance is not a feature of nuclear cataracts. In cortical cataracts, however, the water content rises significantly.
Lens epithelium: site of active transport
The lens is less hydrated and has higher levels of potassium ions (K+) and amino acids than the surrounding aqueous and vitreous humors. Conversely, the lens contains lower levels of sodium ions (Na+), chloride ions (Cl–), and water than its surrounding environment. The cation balance between the inside and outside of the lens is the result both of the permeability properties of the lens cell membranes and of the activity of the sodium-potassium pumps, which reside within the cell membranes of the lens epithelium and each lens fiber. The mechanism of the sodium-potassium pumps, namely pumping sodium ions out while taking potassium ions in, relies on the breakdown of ATP and is regulated by the enzyme Na+,K+-ATPase. Inhibition of Na+,K+-ATPase leads to loss of cation balance and elevated water content in the lens.
The combination of active transport and membrane permeability is often referred to as the pump–leak system of the lens (Fig 3-5). According to the pump–leak theory, potassium and various other molecules, such as amino acids, are actively transported into the lens anteriorly via the epithelium. They then passively diffuse out with the concentration gradient through the back of the lens, where there are no active-transport mechanisms. Conversely, sodium flows in through the back of the lens with the concentration gradient and then is actively exchanged for potassium by the epithelium.
In support of the pump–leak theory, an anteroposterior gradient was found for both ions: potassium was concentrated in the anterior lens; sodium, in the posterior lens. Most of the Na+,K+-ATPase activity is found in the lens epithelium and the superficial cortical fiber cells. The active-transport mechanisms are lost if the capsule and attached epithelium are removed from the lens but not if the capsule alone is removed by enzymatic degradation with collagenase. These findings support the hypothesis that the epithelium is the primary site for active transport in the lens.
Figure 3-5 The pump–leak hypothesis of pathways of solute movement in the lens. The major site of active-transport mechanisms is the anterior epithelium, whereas passive diffusion occurs over both surfaces of the lens.
(Modified with permission from Paterson CA, Delamere NA. The lens. In: Hart WM Jr, ed. Adler’s Physiology of the Eye. 9th ed. Mosby; 1992:365.)
Excerpted from BCSC 2020-2021 series: Section 11 - Lens and Cataract. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.