Anterior polar cataracts in CS rats: a predictor of mature cataract formation.
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PURPOSE: The objective of this study was to characterize the morphology of the anterior opacities formed during recovery from posterior subcapsular cataract (PSC) in Royal College of Surgeons (RCS) rats. METHODS: Lenses from RCS rats at 8 and 12 weeks postnatal (n = 14 and 12, respectively) were examined under a dissecting microscope for the presence of anterior opacities. Lenses with anterior opacities were fixed, embedded in epoxy resin, and sectioned along the optic axis for light microscopy (LM) and transmission electron microscopy (TEM). RESULTS: At eight weeks postnatal, 21.5% of animals (3/14) had anterior cataracts. Light microscopy of 1- to 2-microm-thick sections revealed an anomalous layer of material located at the epithelium-fiber interface, which was identified as a zone of liquefaction by TEM. Epithelial cells had minor structural defects but were not necrotic. Anterior portions of elongating and cortical fibers under the zone of liquefaction were undisrupted, whereas their posterior portions had numerous vacuoles. The anterior opacities were classified as anterior polar cataracts (APCs) based on the location and type of morphologic damage in the affected lenses. At twelve weeks postnatal, 25% of animals (3/12) had APCs that involved prominent vesiculation of the anterior cortex. Ultrastructural examination showed that large vesicles were located between and inside anterior fibers and that most extracellular spaces were abnormally widened. Posteriorly, internalization of the PSC by new fiber growth was disordered and displayed vesiculation and density variations. In the bow region, LM revealed minor structural irregularities that were identified as groups of apparently degenerating fibers by TEM. CONCLUSIONS: APCs in RCS rats are caused by degeneration of elongating fibers in the bow region and subsequent damage in the superficial anterior cortex. The percentage of animals with APCs (25%) was consistent with the percentage of animals in which mature cataracts eventually develop. The morphologic changes, time of onset, and percentage of animals affected suggest that APC is the initial manifestation of mature cataract formation in RCS rats. (+info)
Loss of heterozygosity in pseudoexfoliation syndrome.
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PURPOSE: Pseudoexfoliation (PEX) syndrome is characterized by the accumulation of a material of unknown origin in the anterior structures of the eye. Loss of heterozygosity (LOH) in a genetic locus indicates the presence of a gene located in the same region that could be implicated in the development or the progression of a disease. In this study, the occurrence of LOH in tissues involved in PEX and the possible correlation of LOH incidence with clinical parameters were evaluated. METHODS: Twelve iris specimens, 12 anterior capsule specimens, and respective blood samples were obtained from 17 patients with PEX (13 men), who were undergoing glaucoma and cataract surgery. Sixteen anterior capsule specimens and four iris specimens were obtained from 16 patients without PEX. Polymerase chain reaction was used to amplify 10 highly polymorphic microsatellite markers located on chromosomes 1, 7, 9, and 13. RESULTS: Overall, 83.3% (20/24) of PEX specimens and 94.11% (16/17) of patients with PEX had LOH. The highest incidence of LOH was observed in marker D13S175 (41.6%) followed by D7S478 and D7S479 (37.5%). Only three non-PEX specimens displayed LOH. The number of loci lost was directly related to the altitude of the patients' present residence, but the number lost did not differ significantly between the iris and capsule samples. CONCLUSIONS: The occurrence of LOH in tissues involved in PEX implies a genetic role in PEX pathogenesis at a cellu lar level. The correlation of LOH incidence with the altitude of the patient's residence, could indicate an increased susceptibility to UV radiation of the chromosomal regions examined. (+info)
Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia.
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The biometric, optical and physical properties of 19 pairs of isolated human eye-bank lenses ranging in age from 5 to 96 years were compared. Lens focal length and spherical aberration were measured using a scanning laser apparatus, lens thickness and the lens surface curvatures were measured by digitizing the lens profiles and equivalent refractive indices were calculated for each lens using this data. The second lens from each donor was used to measure resistance to physical deformation by providing a compressive force to the lens. The lens capsule was then removed from each lens and each measurement was repeated to ascertain what role the capsule plays in determining these optical and physical characteristics. Age dependent changes in lens focal length, lens surface curvatures and lens resistance to physical deformation are described. Isolated lens focal length was found to be significantly linearly correlated with both the anterior and posterior surface curvatures. No age dependent change in equivalent refractive index of the isolated lens was found. Although decapsulating human lenses causes similar changes in focal length to that which we have shown to occur when human lenses are mechanically stretched into an unaccommodated state, the effects are due to nonsystematic changes in lens curvatures. These studies reinforce the conclusion that lens hardening must be considered as an important factor in the development of presbyopia, that age changes in the human lens are not limited to the loss of accommodation that characterizes presbyopia but that the lens optical and physical properties change substantially with age in a complex manner. (+info)
Molecular architecture of the lens fiber cell basal membrane complex.
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Lens fiber cells are transparent, highly elongated, epithelial cells. Because of their unusual length these cells represent a novel model system to investigate aspects of epithelial cell polarity. In this study, we examined the fiber cell basal membrane complex (BMC). The BMC anchors fiber cells to the lens capsule and facilitates their migration across the capsule. Confocal microscopy revealed that bundled actin filaments converge beneath the center of each BMC and insert into the lateral membrane at points enriched in N-cadherin. Two other contractile proteins, caldesmon and myosin, were enriched in the BMC, co-localizing with f-actin bundles. The actin/N-cadherin complex formed a hexagonal lattice, cradling the posterior face of the lens. Removal of the capsule caused the tips of the fiber cells to break off, remaining attached to the stripped capsule. This provided a method for assaying cell adhesion and purifying BMC components. Fiber cell adhesion required Mg2+ and/or Ca2+ and was disrupted by incubation with beta1 integrin antibody. BMC proteins were compared with samples from the neighboring lateral membrane. Although some components were common to both samples, others were unique to the BMC. Furthermore, some lateral membrane proteins, most notably lens major intrinsic protein (MIP), were excluded from the BMC. Western blotting of BMC preparations identified several structural proteins originally found in focal adhesions and two kinases, FAK and MLCK, previously undescribed in the lens. These data suggest that the BMC constitutes a distinct membrane domain in the lens. The structural organization of the BMC suggests a role in shaping the posterior lens face and hence the refractive properties of the eye. (+info)
Digital image capture and automated analysis of posterior capsular opacification.
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PURPOSE: To develop and validate a digital imaging and analysis technique for assessing the extent of posterior capsular opacification after cataract surgery. METHODS: Retroillumination images of the posterior capsule were obtained by using a digital camera mounted on a slit lamp. The images were analyzed using an available image analysis software program. The image acquisition and analysis techniques were tested for face validity, reproducibility, and the ability to detect progression of capsular opacity over time. RESULTS: Digital retroillumination images were obtained without patient discomfort. Automated analysis of images correlated well with clinical grading both at slit lamp examination and when looking at the images themselves (Spearman's correlation coefficient >0.7). Analysis of images taken at different times showed high reproducibility (intraclass correlation >0.9), and the system was able to identify progression of capsular opacity over a 2-year period with a mean increase of 15.8% in progressors versus an increase of 0.6% in nonprogressors (P < 0.05). CONCLUSIONS: Digital retroillumination images of the posterior capsule can be obtained reliably, and automated analyses correlate well with clinical assessment. The system presented here uses commercially available instruments and software, and it is practical for use in longitudinal studies of posterior capsule opacification. It is reliable, easy to use, and can detect small changes in the percentage area covered by posterior capsule opacification over time. (+info)
The effect of the haptic portion of intraocular lens on the development of posterior capsular opacification in rabbit.
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Using a white rabbit model, the effect of the haptic portion of the intraocular lens (IOL) and intracapsular ring on the development of posterior capsular opacification (PCO) after extracapsular cataract extraction (ECCE) with phacoemulsification was studied. Implantation of both the intracapsular ring and IOL developed less PCO than implantation of the IOL alone. ECCE followed by implantation of the intracapsular ring alone also developed less PCO than ECCE alone. Through this experimental work in a rabbit model, it could be conceived that the haptic portion of IOL and the intracapsular ring can prevent the development of PCO. (+info)
Uveitis induced by lymphocytes sensitized against a transgenically expressed lens protein.
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PURPOSE: Previously established experimental models for lens-associated uveitis (LAU) are all mediated by antibodies. The present study analyzed the features of a novel experimental intraocular inflammatory eye disease that is mediated by lymphocytes targeted at a lens antigen. METHODS: Conventional technologies were used to generate three lines of transgenic (Tg) mice, expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter. To induce intraocular inflammation, these Tg mice were injected with lymphocytes from syngeneic wild-type donors sensitized against HEL. Before their injection, the cells were stimulated in culture with HEL. To release lenticular material, some eyes were capsulotomized. Ocular histopathologic changes were examined by routine methods. Levels of HEL antibody were measured by enzyme-linked immunosorbent assay, whereas cellular immunity was determined by the lymphocyte proliferation assay. RESULTS: Intraocular inflammation developed in HEL-Tg mice injected with syngeneic lymphocytes sensitized against HEL. The severity of inflammation was directly related to the number of injected cells, as well as to the accessibility of HEL. The most intense inflammation was seen in Tg mice in which the lens was disintegrated due to high production of HEL. In mice with no apparent lenticular changes the inflammation was enhanced by capsulotomy. The inflammation affected all segments of the eye and persisted for at least 39 days after adoptive transfer of cells. Four days after cell injection, the inflammation consisted of subacute infiltration, with both mononuclear and polymorphonuclear leukocytes, whereas more chronic infiltration was seen at later times. Vigorous cellular immunity but no antibody to HEL was found in recipient mice, thus demonstrating the exclusive participation of cellular immunity in the pathogenesis of this experimental disease. CONCLUSIONS: Transgenic mice expressing HEL in their lenses develop intraocular inflammation after injection of syngeneic lymphocytes sensitized against HEL. This experimental disease is a novel cell-mediated model for LAU. (+info)
Lens cell populations studied in human donor capsular bags with implanted intraocular lenses.
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PURPOSE: Posterior capsule opacification is an ongoing cellular redistribution process. The level of viable cell coverage was therefore determined in human donor capsular bags with implanted intraocular lenses, and cellular morphology and ultrastructure were investigated in relation to cell type and level of differentiation. METHODS: Donor capsular bags, retrieved at intervals of 4 months to 13 years after surgery, were investigated by phase optics before fixation. Postfixation techniques included scanning electron microscopy and transmission electron microscopy of sections and immunofluorescent staining of cytoskeletal proteins in wholemounts. RESULTS: All the capsular bags contained a large population of viable cells on the capsular surfaces. Cells on the anterior face of the anterior capsule and in the spaces around the intraocular lens had an elongated morphology and expressed alpha-smooth muscle actin. The cells formed light-scattering, multilayered aggregates and strands that were surrounded by layers of extracellular matrix. The regions between the intraocular lens and the equator of the bags were populated by monolayers of epithelial cells of normal morphology and ultrastructure, on both the anterior and posterior capsules. In some regions the apical surfaces of the two epithelial monolayers were in contact, and in some parts of the equatorial regions, differentiation of cells into well-organized fiberlike cells was evident. CONCLUSIONS: Human capsular bags contain a large population of viable cells for many years after cataract surgery. Cells in the regions around the intraocular lens undergo transition to a mesenchymal type. Cells peripheral to these regions can form a stable closed microenvironment in which both normal epithelial morphology and differentiation to fiberlike cells are maintained. (+info)