Lens Changes Research Articles

Morphogenetic and apoptotic changes in diabetic cataract: Prevention by pyruvate

Studies have been conducted to ascertain the preventive effect of pyruvate against diabetes induced damage to DNA and associated morphogenetic changes in the mouse lens. Such changes were characterized by DNA nicks as well as by gross morphological changes in the nuclei, evident respectively by TUNEL and Hoechst staining procedures. Morphogenetic changes were also apparent by abnormal diferentiation of the germinal epithelial cells and errors in their migratory pathway. These changes were prevented by simultaneous administration of pyruvate to the diabetic animals. The preventive effect of this agent is attributable to its property of scavenging oxy-radicals generated by high levels of the sugars.

Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses

We have examined the gene expression profiles of young, old and cataractous human lenses in order to differentiate those gene expression changes specific for cataract from those also associated with lens aging. Differentially expressed transcripts were identified by oligonucleotide microarray analysis and clustered according to their known functions. Four hundred and twelve transcripts that are increased and 919 transcripts that are decreased were identified at the 2-fold or greater level between epithelia isolated from cataract relative to clear lenses while 182 transcripts that are increased and 547 transcripts that are decreased were identified at the 2-fold or greater level between young and old lens epithelia. Comparison of the cataract gene expression changes with those detected in lens aging revealed that only 3 transcripts exhibited similar trends in gene expression. These data suggest that cataract- and age-specific changes in gene expression do not overlap and provide evidence for multiple cataract- and age-specific gene expression changes in the human lens.

Spatially variant changes in lens power during ocular accommodation in a rhesus monkey eye.

This study investigated the changes in ocular aberrations that occur over the entire lens equatorial diameter during accommodation in iridectomized rhesus monkey eyes to understand the nature of accommodative lenticular deformation. Accommodation was centrally stimulated to a range of different response amplitudes (0 D to approximately 11 D), and ocular aberrations were measured with a Shack-Hartmann wavefront sensor in both eyes of one previously iridectomized 10-year-old rhesus monkey. At the highest amplitude in the two eyes, aberrations were analyzed over entrance pupil diameters ranging from 3 to 8 mm in steps of 1 mm. Root mean square error of the total measured aberrations, excluding defocus, increased systematically with increasing accommodation from about 1 to 3.5 microns. Spherical aberration became systematically more negative, and vertical coma increased significantly in magnitude with accommodation. There was a strong accommodative change in power near the center of the lens and little change in power at the periphery. At the highest accommodative state, decreasing the analyzed entrance pupil diameter from 8 to 3 mm considerably reduced the wavefront error. The greater increase in optical power near the central region of the lens, combined with an accommodative pupillary miosis, would serve to maximize accommodative refractive change while maintaining acceptable image quality.

Magnification changes in scanning laser tomography.

It is important when evaluating glaucomatous optic disc progression in longitudinal images that image magnification remains unchanged. We studied the effect of changed lens power on magnification in scanning laser tomography. The relative contribution to magnification of axial length, eye-scanner distance, and image-to-image scaling was also assessed. A simulated optic disc in a model eye was imaged using the Heidelberg Retina Tomograph. Lens power was alterable by exchanging intraocular lenses (IOL) mounted at the lens plane of the eye to mimic changes in the crystalline lens. IOL power of +20.0D and axial length of 21.5 mm was compatible with emmetropia. The optic disc was imaged through IOLs differing in power (+16.0D to +25.0D) but with axial length kept constant. IOL power was then held constant and imaging was repeated for various axial lengths (17.5-23.5 mm). Model eye-scanner distance was varied with each test sequence. The distances between landmarks on the disc was measured before and after contour lines were exported. Image size varied with IOL power and axial length (r > 0.98; P < 0.0001), with the magnification effect of a +1D increase in lens power equivalent to a third the magnification effect of a 1-mm increase in axial length. Magnification tended to increase with myopia (IOL power > +20.0D) and was accentuated by longer eye-scanner distances. Image-to-image scaling corrected some magnification though this varied with ametropia. Changed lens power, axial length, and eye-scanner distance can affect the size of the optic disc in scanning laser tomography images. The exported contour line partly compensates for changed magnification.

Ophthalmoscopic and morphogenetic changes in rat lens induced by galactose: attenuation by pyruvate.

Investigations have been conducted on the potential of pyruvate, a normal tissue metabolite, in the prevention of cataract formation. Cataract was induced by maintaining young rats on a diet containing 30% galactose. The progress of cataract was monitored by visual inspection and ophthalmoscopic and slit-lamp examinations. The protective effect of pyruvate was assessed by incorporating it in the galactose diet and drinking water. The progress of cataract was substantially thwarted by this dietary regimen. Substantial morphogenetic changes in the lenses of the galactosaemic animals, which by themselves can offer obstruction to light penetration through the lens and scattering, were significantly attenuated. These changes were ascertained by histological detection of errors in cellular differentiation and their migration in unwanted areas. As per previous studies, the pyruvate effect is attributed to its direct effect on the biochemistry of lens related to the inhibition of oxidative stress, as well as to its effect on tissue physiology related to the lifelong process of organogenesis, characteristic of this tissue.

Influence of anesthesia on ocular effects and temperature in rabbit eyes exposed to microwaves.

To investigate the effect of systemic anesthesia on ocular effects and temperature in rabbit eyes exposed to microwaves, one eye each of 43 male pigmented rabbits (Dutch, 1.8-2.2 kg) was exposed at 2.45 GHz for 60-20 min (300 mW/cm2; 108 W/kg), either under anesthesia (ketamine hydrochloride (5 mg/kg) + xylazine (0.23 mg/kg)) or without anesthesia. Changes in the anterior segment were evaluated by image analysis utilizing a Scheimpflug camera, specular microscopy, and a laser flare cell meter. Temperatures within the eye were measured during microwave exposure by a Fluoroptic thermometer. The exposed eyes showed miosis, conjunctival congestion, corneal edema, and an increase in the light scattering of the anterior shallow cortex in the pupillary area of the lens. The group under systemic anesthesia showed much stronger symptoms than those treated without anesthesia. All of the anterior ocular changes disappeared within a week. The highest temperature during exposure was in the vitreous, followed by the anterior chamber, and the retrobulbar cavity of the orbit. The ocular temperatures of the rabbits under systemic anesthesia were 2-9 degrees C higher than those without anesthesia. Body temperature showed an increase of 1 degrees C during the exposure. Acute high intensity microwave exposure temporarily induced anterior segments inflammation and lens changes. The more pronounced ocular effects in the anesthetized rabbits were associated with the significantly higher ocular temperatures in the anesthetized animals. The influence of systemic anesthesia on ocular changes should be considered.

High sensitivity of ocean ridge thermal structure to changes in magma supply: the Galápagos Spreading Center

We explore the physical mechanisms for the observed apparent sensitivity of ridge axis topography and crustal magma systems to small changes in magma supply at intermediate spreading rates. Numerical experiments were carried out to simulate crustal temperature structure of the Galápagos Spreading Center, which spreads at intermediate spreading rates with its various sections appear to have been influenced to different degrees by the nearby Galápagos hotspot. Model results show a strong ‘threshold’ effect: as the crustal thickness decreases from 7.4 km at the 92°W area with an axial high westward to 6.0 km at the 94°W area with a transitional topography, the depth to the top of a magma lens is calculated to increase from 1.7 to 2.5 km. In contrast, at the 97°W area, where crustal thickness is only 5.6 km and a rift valley is present, the model results predict no steady-state magma lens in the crust. These model calculations provide a simple physical explanation for the recent observations along the Galápagos Spreading Center, where abrupt changes in both magma lens and axial morphology occur within a short distance but crustal thickness changes only modestly. Results of this investigation illustrate the critical importance of hotspots in influencing mid-ocean ridge crustal thickness and the associated changes in thermal structure, especially for ridges that spread at the sensitive range of intermediate spreading rates.

Nine-year incidence of lens opacities in the Barbados Eye Studies

Objective To provide 9-year cumulative incidence of age-related lens opacities in a predominantly black population. Design Population-based cohort study, after 9 years of follow-up (n = 2793; 81% participation). Main outcome measures Nine-year cumulative incidence and progression of lens opacities, by type, based on the Lens Opacities Classification System II at the slit lamp. Results Black participants had a higher 9-year incidence of overall lens changes than white participants (age- and gender-adjusted relative risk [RR], 1.8; 95% confidence interval [CI], 1.2–2.8), as well as of cortical opacities (RR, 3.2; 95% CI, 1.7–6.2). In black participants, incidence rates of any cortical and any nuclear opacities were 33.8% and 42.0%, respectively, and higher than for any posterior subcapsular (PSC) opacities (6.3%). The incidence increased with age for all 3 types, and women had a higher risk of cortical and nuclear opacities ( P<0.05). Single cortical opacities were the most frequent type to develop by the 9-year follow-up (23.2%), followed by nuclear-only opacities (17.1%) and mixed opacities (15.3%). Progression rates of pre-existing opacities were 22.0% for cortical, 17.8% for nuclear, and 25.8% for PSC opacities. Conclusions The 9-year follow-up of this cohort indicated a high incidence and progression of cortical and nuclear opacities, highlighting the public health importance of cataract in black populations.

Structural Changes in α-Crystallin and Whole Eye Lens During Heating, Observed by Low-angle X-ray Diffraction

Whole eye lens and α-crystallin gels and solutions were investigated using X-ray scattering techniques at temperatures ranging from 20 °C to 70 °C. In whole lens isolated in phosphate-buffered saline, the spacing of the dominant X-ray reflection seen with low-angle scattering was constant from 20 °C to 45 °C but increased at 50 °C from 15.2 nm to 16.5 nm. At room temperature, the small-angle X-ray diffraction pattern of the intact lens was very similar to the pattern of α-crystallin gels at near-physiological concentration (≈300 mg/ml), so it is reasonable to assume that the α-crystallin pattern dominates the pattern of the intact lens. Our results therefore indicate that in whole lens α-crystallin is capable of maintaining its structural properties over a wide range of temperature. This property would be useful in providing protection for other lens proteins super-aggregating. In the α-crystallin gels, a moderate increase in both the spacing and intensity of the reflection was observed from 20 °C to 45 °C, followed by an accelerated increase from 45 °C to 70 °C. Upon cooling, this effect was found to be irreversible over 11 hours. Qualitatively similar results were observed for α-crystallin solutions at a variety of lower concentrations.

Lens morphometry determined by B‐mode ultrasonography of the normal and cataractous canine lens

To determine axial lens thickness, anterior chamber depth and axial globe length in canine eyes with normal lenses and in eyes with immature, mature, congenital, posterior polar and diabetic cataract. B-mode ultrasonography was performed in 50 normal dogs and, as a prephacoemulsification screening procedure, in 100 dogs with cataract. Axial B-mode ultrasonograms were used to determine lens thickness, anterior chamber depth and globe diameter. Statistical comparisons between groups were made by analysis of variance and multivariate analysis, with a significance level of P < 0.05. Axial globe lengths were not statistically significantly different between groups apart from the smaller globes in younger dogs with congenital cataract. Axial lens thickness in diabetics (8.4 +/- 0.9 mm) was statistically significantly different from the lens thickness in normal eyes (6.7 +/- 1.0 mm), eyes with immature cataract (6.4 +/- 0.8 mm) and eyes with mature cataract (7.4 +/- 0.9 mm) although these groups, while varying in thickness, were not statistically significantly different from each other. Anterior chamber depth was statistically significantly reduced in eyes with diabetic cataract (2.9 +/- 0.1 mm) from that in normal eyes (3.8 +/- 0.1 mm), eyes with immature cataract (3.5 +/- 0.1 mm) and eyes with mature cataract (3.2 +/- 0.6 mm) although these groups, while varying in chamber depth, were not statistically significantly different from each other. Lenses with diabetic cataracts were significantly increased in axial thickness compared to lenses in other eyes, although lenses with mature cataracts showed a trend towards increased axial thickness and immature cataracts demonstrated a trend towards reduced thickness. While previous studies on cataract pathobiology have suggested a reduction in lens thickness in immature cataract through lens protein loss and an increase in thickness in mature cataracts through intumescence, this study is the first to document these changes in the canine lens.

Metabolic changes in rat lens after in vivo exposure to ultraviolet irradiation: measurements by high resolution MAS 1H NMR spectroscopy.

In the present study, high-resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS (1)H NMR) spectroscopy was used to investigate changes in the metabolic profile of intact rat lenses after UVB irradiation of the eyes. Three groups of Sprague-Dawley rats were exposed to UVB radiation at 2.5, 5.0, and 7.5 kJ/m(2). One eye was exposed, and the contralateral eye served as the control. One week after exposure, the lenses were removed and forward light-scattering was quantified. Thereafter, proton NMR spectra from the intact lenses were obtained. Relative changes in metabolite concentrations were determined. The lenses in all three groups showed significant increases in light-scattering after UVB irradiation. The high-quality HR-MAS (1)H NMR spectra permitted more than 30 different metabolites to be identified. UVB irradiation caused a significant decrease (P < 0.05) in concentrations of taurine, hypotaurine, tyrosine, phenylalanine, valine, myo-inositol, phosphocholine, betaine, succinate, and glutathione at all three UV doses. For glycine, glutamate, and lactate, significant decreases in concentration were observed at the two lowest UVR-B doses. The total amount of adenosine tri- and diphosphate and (ATP, ADP) decreased significantly and that of adenosine monophosphate AMP increased significantly at the two highest doses. Alanine was the only amino acid that increased after UVB irradiation. None of these metabolites exhibited a significant UVB dose-dependent relationship. This study demonstrates for the first time the potential of HR-MAS (1)H NMR spectroscopy as an analytical tool for use on intact lenses. Near-threshold UVR-B doses led to a generally significant decrease in water-soluble metabolites 1 week after exposure. The lack of dose-dependent changes in the metabolites indicates that repair processes during the first week after UVB irradiation overcome the immediate metabolic disturbances.

Mesures de champs pour des essais de cisaillement sur des renforts tissés

The mechanical behaviour of dry woven fabrics as composite reinforcements is investigated using optical strain measurements during pure shear tests performed on a picture frame device. This optical measurement technique has many advantages, including the absence of contact with the sample. A change in lens allows measurements at different scales, from a whole sample (macroscopic measurement), to a few unit patterns only (mesoscopic measurement). On top of that, the out of plane displacement may be obtained by a stereoscopic method, using two symmetric points of view. Thus, detailed description of a pure shear test may be conducted, leading us to explain the forming of wrinkles within the woven sample, concluding the test.

Effects of UV-A irradiation on lens morphology and optics

Epidemiological studies have indicated that ultraviolet radiation (UVR) is one of the main factors leading to senile cataract formation. We investigated morphological changes in the eye lens caused by UVR-A. Twenty three pairs of lenses obtained from 23 one-year-old calves were used for this study. For each pair, one lens was exposed to 44 J/m 2 UVR in the 365 nm wavelength region while the contralateral lens was not exposed and served as a control. The lenses were placed in specially designed organ culture containers for pre-incubation. Lenses were exposed to UVR after one day in culture. After irradiation, lens optical quality was monitored throughout additional 15 days of the culture period and lenses were taken for morphological analysis by scanning electron microscopy. Damage to lens optical quality was evident as early as day 8 after the irradiation and increased with time in culture. We found irregularity of fiber morphology in lenses exposed to UV-A irradiation (but not in control lenses), similar to that reported previously for aged lenses. At the end of the culture period (day 16), lens fiber membranes also showed holes in fiber membranes. We conclude that UVR-A caused damage to cell membranes of the lens and alterations in lens optics, which may subsequently lead to senile cataract formation.

The effect of continuous low doses of x-ray irradiation on the rat lens

Purpose: To clarify the morphological changes in the rat lens after irradiation with continuous low doses of x-ray at different intervals. Methods: Male Wistar rats at the age of 8 weeks were irradiated with three doses of 2 Gy at intervals of either 1 week or 1 day. Over the period from the first week to the eighth week after irradiation, the eyeballs of the rats were enucleated progressively and changes in the lenses were examined morphologically. A comparison was made with specimens from control rats at each time of enucleation. Results: (1) Three doses of weekly irradiation: 1 week later, the lens epithelium and fibers at the equator showed mild swelling. Bow configuration was slightly disturbed. Eight weeks later, swelling and uneven height of epithelial cells in the equatorial area, irregular bow configuration, swelling of cortical fibers and epithelial loss and deformed nuclei at the central epithelium were observed. (2) Three doses of daily irradiation: 1 week later, mild changes in the lens such as uneven height of epithelial cells, irregular bow structures, and swelling of cortical fibers were observed. Eight weeks later, irregular bow configuration, posterior dislocation of nuclei, severe epithelial loss and marked swelling of cortical fibers were observed at the equatorial area. Epithelial loss and deformed nuclei of the epithelium were observed in the central area. Conclusion: The lens was damaged by continuous irradiation even though the dose was low. The damage to the lens caused by daily irradiation was more severe than that by weekly irradiation. The main symptoms were degeneration and loss of epithelial cells and swelling of cortical fibers.

Progression of pellucid marginal degeneration and higher-order wavefront aberration of the cornea

Purpose: To report the time course of changes in corneal wavefront aberrations in a patient with pellucid marginal degeneration. Case: A 59-year-old man with pellucid marginal degeneration was followed-up annually with slit-lamp microscopy and videokeratography for 11 years. The anterior corneal height data of the videokeratography were expanded into the set of orthogonal Zernike polynomials to calculate wavefront aberrations for the central 3-mm cornea. Observations: Although the patient complained of gradual deterioration of vision, there was no evident sign of disease progression on slit-lamp examination and visual acuity measurement. Color-coded maps of videokeratography showed slight deterioration over time, but no remarkable and decisive changes were seen. Coma-like aberration displayed a gradual, but apparent increase with a 1.67-fold worsening (0.473 μm to 0.792) during the 11-year follow-up period. Spherical-like aberration remained almost stable throughout the observation period. There were no obvious changes in crystalline lens and retina. Conclusions: The results suggest that increases in coma-like aberrations of the cornea reflect the subclinical progression of pellucid marginal degeneration over the years.

Contact lens complications.

Complications associated with contact lenses range from mild to severe and occur with all lens modalities. Contact lens wear can cause a change in corneal physiology, which can lead to epithelial, stromal, and endothelial compromise. Other complications include lens deposition, allergic conjunctivitis, giant papillary conjunctivitis, peripheral infiltrates, microbial keratitis, and neovascularization. Pre-existing conditions can contribute to these complications, or they can occur in association with contact lens wear and care regimens. Patient-related factors, such as alteration of the recommended wearing or replacement schedules and noncompliance with recommended contact lens care regimens for economic reasons, convenience, or in error, contribute to contact lens-related complications and have led to difficulty in accurate determination of complication rates among the various lens wear modalities. Complications may require discontinuation of contact lenses, topical therapy, and changes in contact lens wearing schedules, materials, and care solutions. On initial lens fitting and follow-up evaluations, practitioners should review contact lens replacement and cleaning regimens with patients and discuss complications. To avoid serious complications, patients should be reminded to remove their contact lenses as soon as ocular irritation occurs, and to call their eye care practitioner immediately if symptoms persist.

Expression patterns for glucose transporters GLUT1 and GLUT3 in the normal rat lens and in models of diabetic cataract.

To determine whether the expression levels and cellular distribution of the facilitative glucose transporters GLUT1 and -3 undergo changes in the hyperglycemic lens. Hyperglycemia was induced in vivo by injecting rats with streptozotocin or in vitro by culturing lenses in the presence of 50 mM glucose. Northern blot analysis and quantitative RT-PCR were used to detect changes in GLUT1 and -3 transcript levels, and Western blot analysis was used to monitor changes in GLUT3 protein expression levels in diabetic rats. Immunocytochemistry was used to map the cellular distribution of GLUT3 in normal and hyperglycemic lenses. GLUT1 and -3 were found to be differentially expressed in the epithelial and fiber cells, respectively. In the fiber cells, the distribution of GLUT3 protein changed as a function of fiber cell differentiation. In young differentiating fiber cells, GLUT3 was mainly found in the cytoplasm, but with increasing depth into the lens became inserted into the narrow sides of older fiber cells, before becoming completely dispersed around the entire membrane of the oldest fiber cells. Hyperglycemia had similar effects on tissue damage and transporter expression in both the in vitro and in vivo models. Tissue damage was characterized by an initial local cell swelling that with prolonged insult gradually spread and resulted in the creation of large areas of tissue liquefaction. Northern blot analysis and quantitative RT-PCR showed that transcript for GLUT3 but not GLUT1 was upregulated under hyperglycemic conditions. This increase in GLUT3 expression was confirmed at the protein level by both Western blot analysis and immunocytochemistry. In hyperglycemic lenses, GLUT3 antibody labeling was localized to the region of tissue liquefaction. GLUT3 in the lens exhibits dynamic changes in expression levels and cellular localization as a function of fiber cell differentiation and hyperglycemia. In the lens cortex, regions of GLUT3 overexpression and hyperglycemic tissue damage overlap, suggesting a functional relationship.

Three-dimensional high-frequency ultrasound and presbyopia

Objective: Presbyopia is the most common refractive disturbance. The aim of this study was to investigate the benefit of 3D ultrasonic imaging in combination with FEM calculations to simulate accommodative processes. These experiments may provide further information about lens changes during accommodation and may lead to a better understanding of the role of the lens and the ciliary body changes in the progression of the presbyopia.

Three-dimensional high-frequency ultrasound and presbyopia

Objective: Presbyopia is the most common refractive disturbance. The aim of this study was to investigate the benefit of 3D ultrasonic imaging in combination with FEM calculations to simulate accommodative processes. These experiments may provide further information about lens changes during accommodation and may lead to a better understanding of the role of the lens and the ciliary body changes in the progression of the presbyopia.

Evaluation of Lenticonus in Alport’s Syndrome: Quantitative Scheimpflug Analysis

Anterior lenticonus is an ocular abnormality that can occur in Alport’s syndrome. In this study, Scheimpflug slit imaging analyses were employed for quantitative and objective evaluation of lens changes associated with Alport’s syndrome. It was determined that while the apices of the lenticular protrusions are central in the vertical plane, they are nasally displaced in the horizontal meridian. The eccentricity and dimensions of the diameters and thicknesses of the conical aberration are highly correlated in both eyes. Lens thickness and anterior chamber depth do not differ between eyes. Densitometrically similar differences are apparent in the cortex and nuclear regions although evidence of overt opacification may or may not be present. The data strongly suggest that the physical parameters of the lenticonus are consistent with the constraints imposed by the pupil. Changes observed in the cornea and the vitreous may be associated with the syndrome.