The lens growth process (original) (raw)
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The Penny Pusher: a cellular model of lens growth
Investigative ophthalmology & visual science, 2014
Purpose:The mechanisms that regulate the number of cells in the lens and, therefore, its size and shape are unknown. We examined the dynamic relationship between proliferative behavior in the epithelial layer and macroscopic lens growth. Methods:The distribution of S-phase cells across the epithelium was visualized by confocal microscopy and cell populations were determined from orthographic projections of the lens surface. Results:The number of S-phase cells in the mouse lens epithelium fell exponentially, to an asymptotic value of ≈200 cells by six months. Mitosis became increasingly restricted to a 300 µm-wide swath of equatorial epithelium, the germinative zone (GZ), within which two peaks in labeling index were detected. Postnatally, the cell population increased to ≈50,000 cells at 4-weeks-of-age. Thereafter, the number of cells declined, despite continued growth in lens dimensions. This apparently paradoxical observation was explained by a time-dependent increase in the surfa...
Experimental Eye Research, 2017
Understanding how tissues and organs acquire and maintain an appropriate size and shape remains one of the most challenging areas in developmental biology. The eye lens represents an excellent system to provide insights into regulatory mechanisms because in addition to its relative simplicity in cellular composition (being made up of only two forms of cells, epithelial and fiber cells), these cells must become organized to generate the precise spheroidal arrangement that delivers normal lens function. Epithelial and fiber cells also represent spatially distinct proliferation and differentiation compartments, respectively, and an ongoing balance between these domains must be tightly regulated so that the lens achieves and maintains appropriate dimensions during growth and ageing. Recent research indicates that reciprocal inductive interactions mediated by Wnt-Frizzled and Notch-Jagged signaling pathways are important for maintaining and organizing these compartments. The Hippo-Yap pathway has also been implicated in maintaining the epithelial progenitor compartment and regulating growth processes. Thus, whilst some molecules and mechanisms have been identified, further work in this important area is needed to provide a clearer understanding of how lens size and shape is regulated.
A thorough comprehension of the biochemical, biometric, optical and physical properties of the human lens, and how these change with age, is essential for understanding the functioning of the eye and the development of age-related visual disorders, such as presbyopia. Many of the required data can only be obtained in vitro, using lenses obtained from eye bank eyes. However, such eyes have generally been stored for several days and their lenses may have become swollen during this time . Because of the difficulty in obtaining fresh human lenses, attempts are sometimes made to extrapolate from animal studies. It is not known whether such extrapolations are always appropriate for modelling human lens properties.
The fate of dividing cells during lens morphogenesis, differentiation and growth
Experimental Eye Research, 2011
Early in development, the ocular lens establishes its distinctive architecture, and this is maintained throughout life as the lens continues to grow. This growth is tightly regulated through the proliferation of the lens epithelial cells and their subsequent differentiation into specialised elongated fiber cells. Although much work has been carried out to define these patterns of growth, very little has been reported on the detailed fate and kinetics of lens cells during embryogenesis. Using BrdU-incorporation, the present study has attempted to follow the fate of lens cells that have undergone at least one round of DNA synthesis during the early stages of lens morphogenesis. Results from this work have confirmed that the rate of lens cell proliferation and new fiber cell differentiation progressively slows as the lens differentiates and grows. In addition, these studies have shown that early in lens development, not all DNA synthesis is restricted to the lens epithelium, with some elongating fiber cells retaining the ability to undergo DNA synthesis. Adopting this system we have also been able to place the initiation of secondary fiber cell differentiation in the mouse lens by E12.5, concomitant with the loss of the lens vesicle lumen by the elongating primary fiber cells. Overall, this study has allowed us to revisit some of the mechanisms involved in early lens development, has provided us with insights into the fate of cells during this rapid phase of murine lens growth, and has provided a novel method to study the rate of new fiber cell differentiation over a defined period of lens development and growth.
A full lifespan model of vertebrate lens growth
Royal Society Open Science, 2017
The mathematical determinants of vertebrate organ growth have yet to be elucidated fully. Here, we utilized empirical measurements and a dynamic branching process-based model to examine the growth of a simple organ system, the mouse lens, from E14.5 until the end of life. Our stochastic model used difference equations to model immigration and emigration between zones of the lens epithelium and included some deterministic elements, such as cellular footprint area. We found that the epithelial cell cycle was shortened significantly in the embryo, facilitating the rapid growth that marks early lens development. As development progressed, epithelial cell division becomes non-uniform and four zones, each with a characteristic proliferation rate, could be discerned. Adjustment of two model parameters, proliferation rate and rate of change in cellular footprint area, was sufficient to specify all growth trajectories. Modelling suggested that the direction of cellular migration across zonal...
Lens growth and internal structure
Growth of the human lens and the development of its internal features are examined using in vivo and in vitro observations on dimensions, weights, cell sizes, protein gradients and other properties. In vitro studies have shown that human lens growth is biphasic, asymptotic until just after birth and linear for most of postnatal life. This generates two distinct compartments, the prenatal and the postnatal. The prenatal growth mode leads to the formation of an adult nuclear core of fixed dimensions and the postnatal, to an ever-expanding cortex. The nuclear core and the cortex have different properties and can readily be physically separated. Communication and adhesion between the compartments is poor in older lenses. In vivo slit lamp examination reveals several zones of optical discontinuity in the lens. Different nomenclatures have been used to describe these, with the most common recognizing the embryonic, foetal, juvenile and adult nuclei as well as the cortex and outer cortex. Implicit in this nomenclature is the idea that the nuclear zones were generated at defined periods of development and growth. This review examines the relationship between the two compartments observed in vitro and the internal structures revealed by slit lamp photography. Defining the relationship is not as simple as it might seem because of remodeling and cell compaction which take place, mostly in the first 20 years of postnatal life. In addition, different investigators use different nomenclatures when describing the same regions of the lens. From a consideration of the dimensions, the dry mass contents and the protein distributions in the lens and in the various zones, it can be concluded that the juvenile nucleus and the layers contained within it, as well as most of the adult nucleus, were actually produced during prenatal life and the adult nucleus was completed within 3 months after birth, in the final stages of the prenatal growth mode. Further postnatal growth takes place entirely within the cortex. It can also be demonstrated that the in vitro nuclear core corresponds to the combined slit lamp nuclear zones. In view of the information presented in this review, the use of the terms foetal, juvenile and adult nucleus seems inappropriate and should be abandoned.
A stochastic model of eye lens growth
Journal of theoretical biology, 2015
The size and shape of the ocular lens must be controlled with precision if light is to be focused sharply on the retina. The lifelong growth of the lens depends on the production of cells in the anterior epithelium. At the lens equator, epithelial cells differentiate into fiber cells, which are added to the surface of the existing fiber cell mass, increasing its volume and area. We developed a stochastic model relating the rates of cell proliferation and death in various regions of the lens epithelium to deposition of fiber cells and lens growth. Epithelial population dynamics were modeled as a branching process with emigration and immigration between various proliferative zones. Numerical simulations were in agreement with empirical measurements and demonstrated that, operating within the strict confines of lens geometry, a stochastic growth engine can produce the smooth and precise growth necessary for lens function.
The mechanism of cell elongation during lens fiber cell differentiation
Developmental Biology, 1982
Lens fiber formation is characterized by extensive cell elongation. Earlier studies have shown that lens cell elongation in vitro can occur in the absence of microtubules and is associated with a proportional increase in cell volume. We have previously suggested that lens fiber cell elongation is directly caused by an increase in cell volume. In this report, lenses from 3-and B-day-old chicken embryos were three-dimensionally reconstructed from serial sections to provide a measure of cell volume and length during various stages of primary and secondary lens fiber formation.
Understanding the normal functioning of the human lens and its role in the development of disorders of vision, such as presbyopia and cataract, requires a thorough knowledge of how the lens grows and how its properties change with age. Many of these properties can be obtained only by studying the isolated organ in vitro. In addition, because of the difficulties in obtaining human tissues, animal lenses are frequently used as models for the human lens. Information is needed for these as well. In this review, current knowledge of lens growth and factors that affect growth are examined in a variety of species. Topics covered include changes in lens weight, dimensions, stiffness and refractive index distribution with age and the influence of other factors such as gender, environment and body size. From these, it has become clear that lens growth is not greatly affected by external influences. Although there are many similarities in the growth of lenses from different species, humans (and probably all primates) have distinctly different growth patterns, with prenatal and postnatal growth having different regulatory mechanisms. As a result, human lens properties are different from those of other species. Unfortunately, many of the published data are unreliable, presumably because of post-mortem changes, making it difficult to extrapolate in vitro observations to the in vivo situation. Figure 7. The relationship between (A) lens diameter and (B) thickness and age. Data were obtained from Glasser and Campbell 19 ( ), Jones and colleagues 20 ( ), Larsen 21 (᭹), Moffatt, Atchison and Pope 22 ( ), Pierscionek and Augusteyn 23 ( ), Rosen and associates 24 ( ), Schacchar 25 , ( ) and Smith 26 ( ). Growth of the lens Augusteyn Figure 11. Refractive index gradients along (A) the equatorial and (B) the sagittal axes for a 27-year-old ( ) and a 63-year-old ( ) lens. The data, which were kindly supplied by Drs C Jones and J Pope, were obtained using MRI. 46