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Hyperglycemia can alter the mechanical properties of tissues through the formation of advanced glycation endproducts in matrix proteins that have long half-lives. We used a custom experimental system and subdomain finite element method to quantify alterations in the regional multiaxial mechanical properties of porcine lens capsules that were cultured for 8 or 14 weeks in high glucose versus control media. Findings revealed that high glucose significantly stiffened the capsules in both the circumferential and the meridional directions, but it did not affect the known regional variations in anisotropy. Such information could be important in the design of both improved clinical procedures and intraocular implants for diabetic patients [DOI: 10.1115/1.2401192] Keywords: hyperglycemia, diabetes, biomechanics, cataracts, type IV collagen

The lens capsule of the eye plays fundamental biomechanical roles in both normal physiological processes and clinical interventions. There has been modest attention given to the mechanical properties of this important membrane, however, and prior studies have focused on 1-D analyses of the data. We present results that suggest that the porcine anterior lens capsule has a complex, regionally dependent, nonlinear, anisotropic behavior. Specifically, using a subdomain inverse finite element method to analyze data collected via a new biplane video-based test system, we found that the lens capsule is nearly isotropic (in-plane) near the pole but progressively stiffer in the circumferential compared to the meridional direction as one approaches the equator. Because the porcine capsule is a good model of the young human capsule, there is strong motivation to determine if similar regional variations exist in the human lens capsule for knowledge of such complexities may allow us to improve the design of surgical procedures and implants. [DOI: 10.1115/1.2401188] Keywords: cataracts, accommodation, biomechanics, stress, stiffness

[gamma]S-crystallin ([gamma]S) is an important human and bovine eye lens protein involved in maintaining the transparency of the eye. By adding small amounts of polyethylene glycol (PEG) to the binary aqueous bovine [gamma]S solutions, we have observed liquid-liquid phase separation (LLPS) at -8[degrees]C and revealed that, in the binary [gamma]S-water system, this phase transition would occur at -28[degrees]C. We have measured both the effect of PEG concentration on the LLPS temperature and protein/PEG partitioning between the two liquid coexisting phases. We use our measurements of protein/PEG partitioning to determine the nature and the magnitude of the [gamma]S-PEG interactions and to quantitatively assess the effectiveness of PEG as a crystallizing agent for [gamma]S. We use our measurements of LLPS temperature as a function of protein and PEG concentration to successfully determine the location of the critical point for the binary [gamma]S-water system. This phase transition cannot be observed in the absence of PEG because it is inaccessible due to the freezing of the system. Our findings indicate that the effective interactions between [gamma]S molecules in the binary [gamma]S-water system are attractive. We compare the magnitude of the attraction found for [gamma]S with the results obtained for the other [gamma]-crystallins for which the critical temperature is located above the freezing point of the system. This work suggests that PEG can be used to reveal the existence of LLPS for a much wider range of binary protein-water systems than known previously. protein | cataract | polyethylene glycol | phase transition | partitioning

We describe a case of congenital cataracts in a newborn whose mother received total parenteral nutrition (TPN) throughout her pregnancy. We discuss the potential mechanisms by which TPN may have been causally linked to cataract formation. European Journal of Clinical Nutrition (2014) 68, 943-945; doi: 10.1038/ejcn.2014.103; published online 28 May 2014, BACKGROUND Adequate maternal nutrition is essential for optimal fetal growth. Maternal malnutrition is associated with intrauterine growth retardation and increased perinatal morbidity and mortality. Total parenteral nutrition (TPN) is indicated [...]

Despite the high prevalence of age-related cataracts, there are currently no known therapies to delay or prevent their occurrence. Studies in humans and rodent models suggest that estrogen may provide protection against age-related cataracts. The discovery of ocular estrogen receptors (ERs) indicates that estrogen protection may result from direct interactions with its receptors in the eye, instead an indirect consequence from effects on another tissue. Studies in our transgenic mouse model validate the concept that estrogen is beneficial for the eye. These mice express ER[DELTA]3, a dominant-negative form of ER[alpha] that inhibits ER[alpha] function. In the ER[DELTA]3 transgenic mice, cortical cataracts spontaneously form in ER[DELTA]3 females after puberty and progress with age. The cataracts initiate in the equatorial region of the lens where the epithelial cells differentiate into elongating fiber cells. Cataract formation can be prevented if the females are ovariectomized before, but not after, sexual maturity. Both male and female ER[DELTA]3 mice develop cataracts after neonatal treatment with the potent estrogen diethylstilbestrol (DES). The incidence of spontaneous and DES-induced cataracts in ER[DELTA]3 mice is 100%, yet these cataracts are absent from the wild-type mice. These data suggest that repression of estrogen action induces cortical cataract formation because estrogen is required to activate the ER[DELTA]3 repressor. Evidence of DES-induced cataracts in the ER[DELTA]3 males as well as the females suggests that estrogen is important in lens physiology in both sexes. The ER[DELTA]3 mice provide a powerful model for assessing the role of estrogen in maintaining the transparency of the lens.

Research points out that deamidation of glutamine and asparagine residues in the reduced gammaS-crystallin alters the surface charge and causes conformational changes in the protein leading to disulfide bonds formation, which, in turn renders gammaS-crystallin insoluble. Data reveal that this water-insoluble high molecular weight protein contributes to human nuclear cataracts.

Results demonstrate that homomeric complexes of the lens protein alphaA-crystallin R116C, in which arginine 116 is substituted with a cysteine rsidue, exhibit higher polydispersity than homomeric complexes of wild-type subunits. Data indicate that polydispersity changes, reduced subunit exchange, and enhanced plasma membrane binding capacity lead to alphaA R116C associated cataract.

Women have a higher incidence of cataracts, and epidemiologic data suggest that the increased risk may be caused by a lack of estrogen in postmenopausal years. We have examined the effects of estrogen on methylnitrosourea (MNU)-induced cataractogenesis in Sprague-Dawley rats. Animals were ovariectomized, injected with MNU, and treated with estradiol or estrone by a continuous-release, subcutaneous Silastic implant, or they received an empty Silastic implant (no hormone). In the no-hormone group, rats developed opaque lenses approximately 6 months after MNU treatment. By 8 months, 74% (14/19) of the no-hormone rats had evident opacity in one or both eyes by simple gross inspection; 58% (22/38) of the eyes in this group were opaque. Estradiol or estrone treatment reduced the incidence of cataractous eyes to 12% or 25%, respectively. Lenses were examined under a dissecting microscope for light transmission. The lenses of the group treated with no hormone had light transmission of 26% [+ or -] 9.2%, whereas lenses from the estradiol-treated animals had light transmission of 72% [+ or -] 5.8%. Histological examination revealed that the anterior cortices of the opaque lenses were disrupted and showed the hallmark signs of age-related cataracts; in addition, some eyes that appeared clear by macroscopic examination showed the early histologic signs of cataractogenesis. It was demonstrated with reverse transcription-PCR that lens cells express both [Alpha] and [Beta] types of estrogen receptor, suggesting that the protective effects of the hormones may be a direct, receptor-mediated phenomenon. Thus, the MNU-treated, ovariectomized rat serves as a model for age-related cataractogenesis, and observation of a clear protective effect of estrogens in this system supports the implications of epidemiologic data.

The Xenopus oocyte pair system was employed to study the functional characteristics of a missense mutation in the human connexin 50 gene (P88S) associated with zonular pulverulent cataract. Xenopus oocytes injected with wild-type connexin 50 cRNA developed gap junctional conductances of about 5 microS 4-7 hrs after pairing. On the other hand, the P88S mutant connexin failed to form functional gap junctional channels when paired homotypically. Only one P88S mutant subunit is needed per gap junctional channel to eliminate channel function.

Expression of human multidrug resistance 3(MDR-3)-P-glycoprotein in transgenic mice produces structural changes in lens membrane which cause cataract. MDR-3 encodes a P-glycoprotein and is regulated by a hamster vimentin promoter. Lens structural damage starts at a late embryonic stage and increases during postnatal lens growth. Immunofluorescence and immunogold labeling indicates that MDR3-Pgp is correlated to plasma membrane.

Abstract Aims--To determine the visual outcome and complications of lens aspiration with intraocular lens implantation in children aged 5 years and under. Methods--The hospital notes of all children aged 5 [...]

Chemical probes were applied to demonstrate that the surface hydrophobicities of cataract-associated Pro23 to Thr (P23T) mutants in human [gamma]D-crystallin (HGD) are inversely related to their solubility. The results provide direct evidence for the important role played by net hydrophobic and anisotropic protein-protein interactions in the aggregation of P23T.