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Background To evaluate the age-related changes in the stiffness of the human lens nucleus in vivo. Methods A total of 78 volunteers with best-corrected visual acuity of 20/20with a mean ± standard deviation intraocular pressure (IOP) of 16 ± 2.5 mmHg were divided into 3 groups of 26. The mean ages of Groups A, B and C were 81 ± 5.5, 44 ± 3.2 and 21 ± 2.5 years, with mean axial lengths of 23.8 ± 0.5 mm, 23.8 ± 0.4 mm and 23.9 ± 0.3 mm, respectively. Using an elastographer, the ultrasound echolucency and elastic strain rate of the lens nucleus of one eye, selected randomly, of each subject were measured three times. The strain rate of the lens cortex could not be assessed. The qualitative differences in the strain rates across the groups were assessed, and differences in the strain rate ratios of the lens nuclei across groups were analysed by one-way ANOVA. Results The strain rates of the lens nuclei of Group A were much lower than those in Groups B and C, as assessed qualitatively; the elastograph images of the lens nuclei of the older group showed a blue colour.The strain rate ratios of the lens nuclei of Groups A, B and C were 0.02 ± 0.08, 0.69 ± 0.12 and 1.95 ± 0.85, respectively. The differences in the lens nucleus strain rate ratios across the groups were statistically significant, with p -values < 0.05. Conclusions Ultrasound elastography demonstrated in vivo that an older age is associated with a statistically significantly lower lens nucleus strain rate ratio and therefore a markedly higher lens nuclear stiffness.

Exploring the genetic basis of congenital cataracts in two families identifies a molecule, lanosterol, which prevents intracellular protein aggregation of various cataract-causing mutant crystallins, and which can reduce cataract severity and increase lens transparency in vivo in dogs. Lanosterol counters cataract formation In a study of the genetic basis of congenital cataract formation in two families, Kang Zhang and colleagues demonstrate that lanosterol, a sterol present naturally in the lens, can prevent intracellular aggregation of various cataract-causing mutant crystallin proteins. The mutations identified in the genetic study impair the function of lanosterol synthase, an enzyme for synthesizing lanosterol. In dogs with naturally occurring cataracts, the application of eye drops containing lanosterol for six weeks reduced cataract severity and increased lens transparency, suggesting that lanosterol or molecules with similar activity might provide an alternative to surgery for the management of cataracts. The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people 1 , and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.

The eye lens of vertebrates is composed of fibre cells in which all membrane-bound organelles undergo degradation during terminal differentiation to form an organelle-free zone 1 . The mechanism that underlies this large-scale organelle degradation remains largely unknown, although it has previously been shown to be independent of macroautophagy 2 , 3 . Here we report that phospholipases in the PLAAT (phospholipase A/acyltransferase, also known as HRASLS) family—Plaat1 (also known as Hrasls) in zebrafish and PLAAT3 (also known as HRASLS3, PLA2G16, H-rev107 or AdPLA) in mice 4 – 6 —are essential for the degradation of lens organelles such as mitochondria, the endoplasmic reticulum and lysosomes. Plaat1 and PLAAT3 translocate from the cytosol to various organelles immediately before organelle degradation, in a process that requires their C-terminal transmembrane domain. The translocation of Plaat1 to organelles depends on the differentiation of fibre cells and damage to organelle membranes, both of which are mediated by Hsf4. After the translocation of Plaat1 or PLAAT3 to membranes, the phospholipase induces extensive organelle rupture that is followed by complete degradation. Organelle degradation by PLAAT-family phospholipases is essential for achieving an optimal transparency and refractive function of the lens. These findings expand our understanding of intracellular organelle degradation and provide insights into the mechanism by which vertebrates acquired transparent lenses. In the eye lens of zebrafish and mice, the phospholipases Plaat1 and PLAAT3, respectively, are essential for macroautophagy-independent organelle degradation that produces an organelle-free zone and achieves optimal transparency.

Analyzing stable isotopes in archival tissues, such as fish eye lenses, is used to document shifts in feeding ecology, diet, habitat use, and to reconstruct life history. Fish eye lenses grow throughout their ontogeny, forming multiple sequential layers, or laminae. These laminae represent the chronology of the fish’s life, much like tree rings, which record environmental conditions over time. Lenses are protein-rich, which makes them an ideal structure for analyzing light isotopes such as δ¹³C, δ¹⁵N, and δ 34 S. These light isotopes are primarily integrated into the lens tissue through the fish’s diet, where they are bound to amino acid structures during protein synthesis. As research begins to emerge using eye lenses to reconstruct the life histories of fishes, the need for a reproducible method of delamination grows. For this study, each researcher independently delaminated one lens from each of the 10 adult Chinook Salmon ( Oncorhynchus tshawytscha ). Lens lamina number, diameter (mm), and mass (mg) of each lamina were recorded. Laminae were then submitted for stable isotope analysis of both δ¹³C and δ¹⁵N. Isotope values were used as a validation to compare delamination patterns between researchers. δ¹³C and δ¹⁵N values from the lenses were then plotted using both the assigned lamina number and lens diameter to compare the difference between researchers. Analysis based on lamina number showed significant shifts in isotope values and variability in lamina counts between researchers. However, when lens diameter was used instead of lamina number, isotope patterns throughout the lenses of the same fish were nearly identical. Using lens diameter removes subjectivity between researchers, thereby increasing the reproducibility of the technique and providing a more robust interpretation of the data.

Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.

The purpose of the lens is to project a sharply focused, undistorted image of the visual surround onto the neural retina. The first pre-requisite, therefore, is that the tissue should be transparent. Despite the presence of remarkably high levels of protein, the lens cytosol remains transparent as a result of short-range-order interactions between the proteins. At a cellular level, the programmed elimination of nuclei and other light-scattering organelles from cells located within the pupillary space contributes directly to tissue transparency. Scattering at the cell borders is minimized by the close apposition of lens fibre cells facilitated by a plethora of adhesive proteins, some expressed only in the lens. Similarly, refractive index matching between lens membranes and cytosol is believed to minimize scatter. Refractive index matching between the cytoplasm of adjacent cells is achieved through the formation of cellular fusions that allow the intermingling of proteins. Together, these structural adaptations serve to minimize light scatter and enable this living, cellular structure to function as ‘biological glass’.

Chylack, L. T., Jr., Peterson. L. E., Feiveson, A. H., Wear, M. L., Manuel, F. K., Tung, W. H., Hardy, D. S., Marak, L. J. and Cucinotta, F. A. NASA Study of Cataract in Astronauts (NASCA). Report 1: Cross-Sectional Study of the Relationship of Exposure to Space Radiation and Risk of Lens Opacity. Radiat. Res. 172, 10-20 (2009). The NASA Study of Cataract in Astronauts (NASCA) is a 5-year longitudinal study of the effect of space radiation exposure on the severity/progression of nuclear, cortical and posterior subcapsular (PSC) lens opacities. Here we report on baseline data that will be used over the course of the longitudinal study. Participants include 171 consenting astronauts who flew at least one mission in space and a comparison group made up of three components: (a) 53 astronauts who had not flown in space, (b) 95 military aircrew personnel, and (c) 99 non-aircrew ground-based comparison subjects. Continuous measures of nuclear, cortical and PSC lens opacities were derived from Nidek EAS 1000 digitized images. Age, demographics, general health, nutritional intake and solar ocular exposure were measured at baseline. Astronauts who flew at least one mission were matched to comparison subjects using propensity scores based on demographic characteristics and medical history stratified by gender and smoking (ever/never). The cross-sectional data for matched subjects were analyzed by fitting customized non-normal regression models to examine the effect of space radiation on each measure of opacity. The variability and median of cortical cataracts were significantly higher for exposed astronauts than for nonexposed astronauts and comparison subjects with similar ages (P  =  0.015). Galactic cosmic space radiation (GCR) may be linked to increased PSC area (P  =  0.056) and the number of PSC centers (P  =  0.095). Within the astronaut group, PSC size was greater in subjects with higher space radiation doses (P  =  0.016). No association was found between space radiation and nuclear cataracts. Cross-sectional data analysis revealed a small deleterious effect of space radiation for cortical cataracts and possibly for PSC cataracts. These results suggest increased cataract risks at smaller radiation doses than have been reported previously.

Gap junctions establish direct pathways for cell-to-cell communication through the assembly of twelve connexin subunits that form intercellular channels connecting neighbouring cells. Co-assembly of different connexin isoforms produces channels with unique properties and enables communication across cell types. Here we used single-particle cryo-electron microscopy to investigate the structural basis of connexin co-assembly in native lens gap junction channels composed of connexin 46 and connexin 50 (Cx46/50). We provide the first comparative analysis to connexin 26 (Cx26), which—together with computational studies—elucidates key energetic features governing gap junction permselectivity. Cx46/50 adopts an open-state conformation that is distinct from the Cx26 crystal structure, yet it appears to be stabilized by a conserved set of hydrophobic anchoring residues. ‘Hot spots’ of genetic mutations linked to hereditary cataract formation map to the core structural–functional elements identified in Cx46/50, suggesting explanations for many of the disease-causing effects. Cryo-electron microscopy structures of connexin channels composed of connexin 46 and connexin 50 in an open-state reveal features that govern permselectivity and the location of mutated residues linked to herediatry cataracts.

Purpose: To analyze crystalline lens decentration and tilt in eyes with different axial lengths (ALs) using a swept-source anterior segment optical coherence tomography (SS-AS-OCT). Methods: Patients with normal right eyes who visited our hospital between December 2020 and January 2021 were included in this cross-sectional study. Data on crystalline lens decentration and tilt, AL, aqueous depth (AD), central corneal thickness (CCT), lens thickness (LT), lens vault (LV), anterior chamber width (ACW), and angle κ were collected. Results: A total of 252 patients were included and divided into normal (n = 82), medium-long (n = 89), and long (n = 81) AL groups. The average age of these patients was 43.63 ± 17.02 years. The crystalline lens decentration (0.16 ± 0.08, 0.16 ± 0.09, and 0.20 ± 0.09 mm, P = 0.009) and tilt (4.58° ± 1.42°, 4.06° ± 1.32°, and 2.84° ± 1.19°, P < 0.001) were significantly different among the normal, medium, and long AL groups. Crystalline lens decentration was correlated with AL (r = 0.466, P = 0.004), AD (r = 0.358, P = 0.006), ACW (r = −0.004, P = 0.020), LT (r = −0.141, P = 0.013), and LV (r = −0.371, P = 0.003). Crystalline lens tilt was correlated with age (r = 0.312, P < 0.001), AL (r = −0.592, P < 0.001), AD (r = −0.436, P < 0.001), ACW (r = −0.018, P = 0.004), LT (r = 0.216, P = 0.001), and LV (r = 0.311, P = 0.003). Conclusion: Crystalline lens decentration was positively correlated with AL, and tilt was negatively correlated with AL.

Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial-mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFβ2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.