Lens Suture Research Articles

Age-Dependent Lens Changes in Galactose-Fed Dogs

Aldose reductase initiated sugar cataract formation in 9-month old galactose-fed dogs has been documented to progress from an accentuation of lens sutures (1 month after initial feeding) to the appearance of cortical vacuoles (3 months), cortical opacities (4–6 months) and eventually the progressive formation of a clear zone at the cortical equatorial regions of the cataractous lenses (>12 months). Here, the effect of age on the onset and degree of sugar cataract formation has been investigated in beagles fed a 30% galactose diet starting at 2, 6, and 24 months of age. Cataract formation was monitored by slit lamp and retroillumination microscopy. Compared to 9-month old dogs, cataract formation in the younger dogs was more rapid and the lens changes were more severe. In the 2-month old group of dogs, galactose-feeding resulted in a rapid formation of dense cataracts which began to resorb after 106 days of galactose feeding with only opaque nuclear remnants remaining after eight months. These changes were mirrored by age-dependent reductions of lenticular NADPH-dependent reductase activity.

FGF receptor-1 (flg) expression is correlated with fibre differentiation during rat lens morphogenesis and growth.

Our previous studies indicate an important role for fibroblast growth factor (FGF) in lens development. Here we study the expression of the flg variant of FGF receptor 1 (FGFR1) during lens development by immunohistochemistry and in situ hybridisation. FGFR1 was expressed throughout lens development. Prominent FGFR1 immunoreactivity was associated with cell nuclei, particularly in differentiating lens fibres, suggesting internalisation and nuclear translocation of the receptor. FGFR1 immunoreactivity was also associated with basolateral membranes of cells in the equatorial region and at lens sutures. FGFR1 mRNA was only weakly expressed during early lens morphogenesis but expression increased with the onset of lens fibre differentiation. Once the lens acquired its distinct polarity, an anteroposterior gradient in both protein reactivity and mRNA signal was evident. Anteriorly, central epithelial cells showed weak expression for FGFR1, whereas more posteriorly, in the germinative and transitional zones of the lens where cells maximally proliferate and undergo early stages of fibre differentiation, respectively, expression was significantly stronger. The anteroposterior gradient of increased expression of FGFR1 in the lens coincides with the previously documented anteroposterior gradient of FGF stimulation. In lens epithelial explants, FGF stimulation was found to upregulate FGFR1 expression. Such upregulation may be an important mechanism for generating a high level of FGF stimulation and ensuring a fibre differentiation response. In postnatal rat lenses, there was a significant age-related decline in FGFR1 expression; this correlates with the reduced rate of lens fibre differentiation with age. Overall, these studies support the hypothesis that FGF and FGFR1 are important for regulation of lens fibre differentiation throughout lens development.

The development of lens sutures

The development of lens sutures

The Interrelationship of Lens Anatomy and Optical Quality II. Primate Lenses

We have quantified the influence of lens sutural anatomy on optical quality (focal length variability, i.e. spherical aberration) in adult monkeys (Macaque nemestrina). Adult lenses (n = 6) were initially scanned by a low-power helium-neon laser beam that was passed at a series of acute angles to, and/or directly through, lens sutures. Optical analysis showed that while the 'star' sutures of primate lenses exerted a quantifiable negative effect on focal length variability, this detrimental effect was far less significant than that attributable to 'line' and 'Y' sutures in non-primate lenses. Correlative morphological and 3-D computer-assisted drawing (CAD) analysis of the laser-scanned lenses areas, as well as of variably aged lenses (n = 30), revealed that primates have a more complex lens architecture than non-primates. Non-primate lenses feature suture planes, aligned along the visual axis that are responsible for a significant quantifiable increase in spherical aberration. Primate lenses are characterized by an absence of continuous suture planes aligned along the visual axis. Rather, 3-D-CADs of primate lenses demonstrate that distinct generations of progressively more complex sutures are produced as a function of development, growth, and age. In succession, 'Y' sutures (three branches) are formed throughout embryonic development, 'simple star' sutures (three-six branches) evolve after birth and through infancy, 'star' sutures (six-nine branches) are made in young adult lenses and, finally, 'complex star' sutures (nine-15 branches) are laid down from middle through old age. In view of the fact that slit-lamp evaluation of cataractous lenses often reveals abnormally thin zones of discontinuity, it is significant to note that the temporal development of the zones of discontinuity in normal human lenses is essentially identical to the progressive iteration of offset monkey lens sutures. In conclusion, these studies describe a specific structural aspect of lenses that adversely influences optical quality, and relates it to the most commonly employed clinical technique to identify and monitor the progress of cataracts.

The zones of discontinuity in the human lens: Development and distribution with age

Statistical analysis of Scheimpflug images from the crystalline lenses of 100 emmetropic human subjects ranging in age from 18 to 70 yr confirms that specific zones of discontinuity are a function of lens development and growth. At and beyond the age of 40 yr, as many as four sharply demarcated and complementary zones are seen within the anterior and posterior lens cortex. The locations of the inner edges of the anterior cortical zones of discontinuity were characterized relative to the central sulcus of the lens. Consecutively from the central sulcus, the distances were 1.094, 1.415, 1.695, and 1.994 (± 0.11 mm). Since nuclear thickness in the adult lens is age-independent and the rate of cortical growth has been characterized, the location of the inner margins of the zones are indicative of the age at which they originated; these ages were 4 (± 1 yr), 9 (± 2 yr), 19 (± 4 yr), and 46 (± 10 yr). All of the zones become broader along the outer margin and more dense upon aging, with specific zones appearing to merge in older presbyopic lenses. While lens fetal nuclear transparency decreases with age, it does not feature zones of discontinuity; instead, symmetrically amorphous regions appear centrally in the anterior and posterior nucleus. This demonstration of the onset of specific zones of discontinuity in emmetropic individuals, at defined periods of lens growth that are synchronous the production of successively more complex lens sutures, strongly suggests a causal relationship between lens sutures and the zones of discontinuity.

3D CAD reconstructions of lens suture planes within specific zones of discontinuity from primate lenses

How nestling birds respond to stressful situations may constitute an important survival component that has lasting developmental effects on the hypothalamic pituitary adrenal (HPA) axis. As birds are exposed to increasing amounts of potential anthropogenic stressors through land use change, understanding how these factors contribute to HPA development is important. We examined whether conditions experienced during the nestling stage affected free-living American Kestrel (Falco sparverius) HPA activity prior to fledging. Kestrels experienced varying levels of human disturbance around their nest and we classified this environmental exposure as high or low environmental human disturbance based on traffic patterns and land use. We then exposed some broods from high and low disturbance areas to a standardized disturbance protocol. Prior to fledging we collected blood samples from 25-day-old nestlings immediately after capture and 15 min post-capture. Corticosterone (CORT) did not vary with environmental human disturbance levels, disturbance protocol treatment, or with an interaction between environmental human disturbance and disturbance protocol treatment suggesting that nestling kestrels may not perceive external conditions related to human disturbance as stressful or kestrels may acclimate to disturbance. We also compared the relative effects of environmental human disturbance outside the nest cavity, conditions within the nest cavity (brood size), and individual condition (nestling fat scores) on baseline and stress-induced CORT. Baseline CORT did not vary with human disturbance level, brood size or fat score. Fat scores best explained stress-induced CORT with nestlings in better condition displaying elevated CORT. These results suggest that individual variation is more likely to explain HPA development compared to nest conditions or the external environment. This study demonstrates the importance of considering the effects of developmental conditions on the stress response at several scales.

Die Wirkung von intraokulär appliziertem Azetylcholin und Carbachol auf das postoperative Druckverhalten nach Kataraktoperationen

In a consecutive series of 90 patients we examined the effect of intracameral acetylcholine and carbachol on intraocular pressure following extracapsular cataract surgery. In all cases phacoemulsification and implantation of a folded polyhema intraocular lens under healon was performed. After evacuation of the viscoelastic substance from the capsular bag behind the inserted lens and wound suturing we instilled 0.5 ml 1% acetylcholine, 0.5 ml 0.01% carbachol or 0.5 ml balanced salt solution respectively into the anterior chamber. Without the influence of antiglaucomatous drugs applanation tonometry was performed 6 and 18 hours postoperatively. When compared with preoperative values intraocular pressure decreased in the carbachol group (-2.8 mm Hg) but increased in the acetylcholine group (+0.6 mm Hg) and control group (+4.7 mm Hg). 18 hours postoperatively the mean change was -3.0 mm Hg in the carbachol group, +0.8 mm Hg in the acetylcholine group and +2.3 mm Hg in the control group. Intraocular pressure exceeding 22 mm Hg at 6 hours was observed in 33% of the control group and 13% of the acetylcholine group but none of the carbachol group. At 18 hours intraocular pressure was still elevated in 13% of the control group, 10% of the acetylcholine group and 3% of the carbachol group. Reviewing our results we conclude that the evacuation of viscoelastic substances from the capsular bag behind the implanted lens reduces the incidence of pressure rises in the early postoperative period. This effect can be enhanced by the use of acetylcholine and, the more potent, carbachol.

Confocal microscopy of the in‐situ crystalline lens

The fine structure of the in-situ rabbit crystalline ocular lens from the ex-vivo rabbit eye was observed with a confocal scanning laser microscope in the scattered light mode. The images were observed through the full thickness of the cornea and aqueous humour to a depth of 50 microns in the anterior ocular lens. The following structures were observed from optical sections of the ocular lens: two concentric regions of the lens capsule, epithelial cells, lens sutures, and surface and interior regions of individual lenticular fibres. The observed lateral resolution of the microscope objective was degraded by imaging across thick (millimetre) structures. This study shows the feasibility of obtaining high-contrast images of transparent objects across 1.7 mm of ocular tissue (cornea and aqueous humour) using confocal light microscopy.

Lamellar separation in the human lens: the case for fibre folds. A combined in vivo and electron microscopy study.

Lamellar separation is seen as parallel lines in the lens cortex. It has been the subject of a joint study between Oxford and Amsterdam. The condition was studied in vivo by macro photography and in vitro by scanning electron microscopy. The lines are seen to run concentric with the lens equator, crossing the lens fibres at right angles. The lines are commonly limited by a spoke cataract, a water cleft, or a lens suture. The line may continue beyond these features with a change in direction. The lines may branch and rejoin. The lines extend in depth into the lens, polarised light showing that the lines are due to reflection. The name 'lamellar separation' implied that the appearance is due to separation between the lens lamellae. Lamellar separation is now shown by electron microscopy to be due to folds crossing the lens fibres. The clinical study showed the lines occurring with spoke cataract and the electron microscopy showed the association with the novel finding of peripheral breaks in the fibres. A new name 'Fibre Folds' is proposed.

An estimate of the size and shape of the human lens fibre in vivo.

The size and shape of the lens fibres were estimated by specular reflex photography. The fibres were measured in three separate regions. Peripheral fibres have a mean width of 10.2 micron, the central fibres 11.9 micron, and the central fibres with suture 15.8 micron. Measurements were made of the taper (becoming narrower towards the suture) and flare (becoming wider towards the suture). The peripheral fibres have a mean taper of 0.3 micron per 100 micron. The central fibres have a mean flare of 0.6 micron per 100 micron, and the central fibres with suture have a mean flare of 2.4 micron per 100 micron. These differences are highly significant (p less than 10(-6]. From these measurements the overall shape of the average lens fibre was estimated. This fibre tapers as it passes forward from the equator to the peripheral extent of the lens sutures and then flares increasingly as the junction with the lens suture is approached. A mean increase in peripheral lens fibre width with age at 0.028 micron per year was demonstrated. This is significant (p = 0.042). No difference in fibre width was found in diabetics and non-diabetics.

Cataractogenesis: Developmental Inputs and Constraints

The developmental period during which the lens is susceptible to one or another cataractogenic influence, the types of cataracts that result, and the spatial and temporal patterns in which these cataracts become manifest are better understood in the context of the orderly sequence of steps by which the vertebrate lens develops. Thus, events attending lens induction, formation of the lens vesicle, deposition of the lens capsule, maturation of lens fibers, elaboration of lens sutures, and developmental changes in the relationship of the lens to the optic cup have implications for cataractogenesis. We have also seen that events in juxtalenticular tissues (eg, the zonule, the temporary hyaloid-lenticular vascular, the neural retina) can contribute to the development of lenticular opacities. Hereditary cataracts, as well as congenital cataracts produced in response to untoward environmental input, can be properly understood only within a dynamic developmental context.

Echothiophate cataracts in monkeys. Electron microscopy and microradiography.

• Anterior and posterior subcapsular cataracts were induced in cynomolgus monkeys by topical treatment with echothiophate iodide. The lenses were then studied by light and electron microscopy and by quantitative microradiography. Microradiography revealed foci of swollen lens fibers and reduced protein concentration in the anterior-most and posterior-most 0.3 mm of cortex. By electron microscopy, focal areas of the lens epithelium and the anterior and posterior subcapsular cortex demonstrated enlarged intercellular spaces containing cell membrane fragments and amorphous material. The cortical abnormalities were most frequent at or near the lens sutures. The microradiographic and electron microscopic abnormalities in the cortex corresponded in location, distribution, and optical properties to the vacuoles and solid-appearing opacities seen biomicroscopically in vivo. The mechanism for the increased hydration of the lens caused by cholinesterase inhibitors remains unknown.

Cataracts in the aging rat lens. Morphology and acid phosphatase histochemistry of incipient forms

The present investigation deals with morphological and certain histochemical changes that precede and accompany cataracts associated with aging in the rat. The cataracts were of two types: supranuclear (SNC) and posterior subcapsular (PSC). The initial biomicroscopie lesions, which were associated with the auterior and posterior lens suture systems, respectively, were attributed to cytological alterations of the ends of the superficial fiber cells. Cortical alterations common to both types of cataract included segmental cellular swelling, and the formation of assorted globular and multilamellar inclusions. With SNC, large multilamellar bodies corresponded to anterior sutural vacuolar opacities; while swelling and dissociation of the fiber cell bodies were associated with the formation of lamellar separations, lesions which eventually appeared in the peripheral cortex. Posterior subcapsular intercellular vacuoles, many of which developed a lamellated outer structure, were characteristic of the early form of PSC. An acid phosphataso which served as a marker for lysosomal hydrolases was demonstrated in the intercellular spaces of lenses with early forms of degeneration. The major source of the extracellular enzyme appeared to be the Golgi/lysosomal system within the epithelium and cortex, although the cortical smooth endoplasmic reticulum was not ruled out. Our studies support the concept that the swelling and degeneration of cortical fibers occurring in the initial stages of the cataracts might have been caused by intercellularly located hydrolases. The value of the aged rat lens as a model for human senile cataract was reinforced by the many similarities between the murine and human forms of the disease.

Age changes in the eyes of the Beagle dog.

ABSTRACTChanges with age in the eyes of Beagle dogs are described clinically and histologically. Lenticular changes involve increased prominence of the posterior lens sutures and opacity within the fetal nucleus. Cystoid degeneration of the retina was found in 85% of 8–year–old animals examined. A pigmentary change of the retina was found to be associated with focal degenerative change of the tapetum. No case of retinal atrophy was recorded.