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

Abstract

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.

Signaling and Gene Regulatory Networks in Mammalian Lens Development

“…The outer surface of the lens is covered by a thick extracellular matrix (ECM), the lens capsule, which possesses a range of functions for cell signaling and lens accomodation [12]. Lens transparency and refractive properties depend upon a high accumulation of crystallin proteins in the lens fiber cells that remain water-soluble even when their concentration within the lens “nucleus” reaches 450 mg/ml [13]. Finally, a degradation of mitochondria, endoplasmatic reticula, Golgi apparatuses, and nuclei, within the central fiber cell compartment, the organelle free zone, is needed to minimize light scatterning [14].…”

“…Even though formation of the OFZ eliminates nearly all vital functions of living cells, the mature lens fiber cells undergo a series of remodeling steps and are ultimatelly transformed into a functional “biological glass” [14]. For example, fiber cell compaction concentrates proteins to levels above 450 mg/ml in the central lens fibers and protein gradient across the lens is needed for correction of spherical aberration [13]. In summary, lens as a tissue employs a range of biophysical solutions to meet multiple demands on its mechanical and optical functions for which evolution found numerous elegant solutions [14].…”

The lens growth process

“…This phenomenon is believed to reflect the time-dependent compaction of fiber cells in the lens interior. The precise mechanism of cellular compaction remains elusive but the net effect is to extract water from the cytosol of the inner fibers, leading to the concentration of residual protein (Bassnett and Costello, 2016). Importantly, the establishment of intra-lenticular protein gradients (Philipson, 1969) underlies the internal refractive index gradient of the lens, serving to both augment the focusing power of the lens and correct for longitudinal spherical aberration (Pierscionek and Regini, 2012).…”

“…Because of the continuous addition of newly formed fibers to the lens surface, the lens radius increases over time. However, the rate of macroscopic growth reflects a balance between fiber cell deposition at the surface and compaction of extant cells in the lens interior (Bassnett and Costello, 2016). …”

“…Model simulations are close to measured values at early stages, but there is an increasing discrepancy between simulations and empirical measurements at later time points, with the model predicting an aged lens that is much larger than actually measured (Figure 15B). The most plausible explanation for the discrepancy is that cells in the living lens become compacted over time (Bassnett and Costello, 2016). While there is a convincing body of evidence data to suggest that compaction is a real phenomenon in the lens, there is very little data on the spatial and temporal details.…”