Acute cataract by a high-intensity focused ultrasound procedure: a case report.

BACKGROUND: We report a case of acute onset of cataract after eyelid rejuvenation tightening with intense focused ultrasound (IFUS) treatment without using a protection device. CASE PRESENTATION: A 47-year-old female patient presented at the outpatient clinic with blurred vision in her left eye immediately after undergoing an eyelid tightening procedure, using IFUS, seven days prior. The patient had decreased vision in her left eye, caused by an acute cataract with several drop-like opacities and a rosette-like posterior subcapsular cataract. One month after her first visit, the patient's visual acuity in her left eye decreased to 20/630. A Swept-Source Anterior Segment optical coherence tomography confirmed that the posterior capsule was not ruptured. The patient underwent uneventful phacoemulsification cataract surgery with intraocular lens implantation, which resulted in full visual recovery. CONCLUSIONS: This case emphasized the need to evaluate possible ocular side effects, resulting from periocular IFUS without a protection device, including severe cataract requiring surgery.

Roles of TGF ß and FGF Signals in the Lens: Tropomyosin Regulation for Posterior Capsule Opacity.

Transforming growth factor (TGF) ß and fibroblast growth factor (FGF) 2 are related to the development of posterior capsule opacification (PCO) after lens extraction surgery and other processes of epithelial⁻mesenchymal transition (EMT). Oxidative stress seems to activate TGF ß1 largely through reactive oxygen species (ROS) production, which in turn alters the transcription of several survival genes, including lens epithelium-cell derived growth factor (LEDGF). Higher ROS levels attenuate LEDGF function, leading to down-regulation of peroxiredoxin 6 (Prdx6). TGF ß is regulated by ROS in Prdx6 knock-out lens epithelial cells (LECs) and induces the up-regulation of tropomyosins (Tpms) 1/2, and EMT of LECs. Mouse and rat PCO are accompanied by elevated expression of Tpm2. Further, the expression of Tpm1/2 is induced by TGF ß2 in LECs. Importantly, we previously showed that TGF ß2 and FGF2 play regulatory roles in LECs in a contrasting manner. An injury-induced EMT of a mouse lens as a PCO model was attenuated in the absence of Tpm2. In this review, we present findings regarding the roles of TGF ß and FGF2 in the differential regulation of EMT in the lens. Tpms may be associated with TGF ß2- and FGF2-related EMT and PCO development.

FGF2 antagonizes aberrant TGFß regulation of tropomyosin: role for posterior capsule opacity.

Transforming growth factor (TGF) ß2 and fibroblast growth factor (FGF) 2 are involved in regulation of posterior capsule opacification (PCO) and other processes of epithelial-mesenchymal transition (EMT) such as cancer progression, wound healing and tissue fibrosis as well as normal embryonic development. We previously used an in vivo rodent PCO model to show the expression of tropomyosin (Tpm) 1/2 was aberrantly up-regulated in remodelling the actin cytoskeleton during EMT. In this in vitro study, we show the Tpms family of cytoskeleton proteins are involved in regulating and stabilizing actin microfilaments (F-actin) and are induced by TGFß2 during EMT in lens epithelial cells (LECs). Importantly, we found TGFß2 and FGF2 played contrasting roles. Stress fibre formation and up-regulation of α-smooth muscle actin (αSMA) induced by TGFß2 could be reversed by Tpm1/2 knock-down by siRNA. Expression of Tpm1/2 and stress fibre formation induced by TGFß2 could be reversed by FGF2. Furthermore, FGF2 delivery to TGFß-treated LECs perturbed EMT by reactivating the mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) pathway and subsequently enhanced EMT. Conversely, MEK inhibitor (PD98059) abated the FGF2-mediated Tpm1/2 and αSMA suppression. However, we found that normal LECs which underwent EMT showed enhanced migration in response to combined TGFß and FGF2 stimulation. These findings may help clarify the mechanism reprogramming the actin cytoskeleton during morphogenetic EMT cell proliferation and fibre regeneration in PCO. We propose that understanding the physiological link between levels of FGF2, Tpm1/2 expression and TGFßs-driven EMT orchestration may provide clue(s) to develop therapeutic strategies to treat PCO based on Tpm1/2.

Progressive hyperopic refractive changes after posterior capsule tear following blunt ocular trauma.

Purpose: To describe the mechanism of progressive hyperopia and its management in the long-term course of traumatic cataract with a posterior capsule tear (PCT) following blunt ocular trauma. Observation: A 37-year-old woman presented with blurry vision and photophobia after being hit in the right eye by a slipper. She was found to have PCT with the formation of a traumatic cataract with emmetropia (0 diopters [D]). Three years after the injury, a broader hyperopic change of +8.0 D was found in the patient at her first visit to our clinic. Optical coherence tomography (OCT) analysis of the anterior segment of the eye revealed damage to the posterior capsule and cataracts due to disorganization of the lens fibers and liquefaction of the lens. Femtosecond laser-associated cataract surgery was performed for anterior capsulotomy and segmentation of the nucleus without further enlargement of the PCT, facilitating the placement of a capsular tension ring segment and a multifocal intra ocular lens (IOL) in the capsular bag. At 1-month post-operation, her uncorrected visual acuity was 20/20 in the right eye, with a well-centered IOL. Conclusions and Importance: Isolated PCT due to blunt trauma is rare, and there have been no reports of progressive hyperopia after three years of follow-up. In such cases, the lens may liquefy, resulting in decreased refraction and significant hyperopia.

Orientation of the intermediate-vision zone of rotationally asymmetric multifocal intraocular lenses and photic phenomena.

PURPOSE: To evaluate the association between the orientation of the intermediate-vision zone and postoperative photic phenomena in eyes implanted with rotationally asymmetric multifocal intraocular lenses with + 1.5 diopters near addition. STUDY DESIGN: Retrospective comparative case series. METHODS: We performed the photic phenomena test (PPT) to quantitatively evaluate photic phenomena at 1-3 months after cataract surgery with Lentis Comfort LS-313 MF15 or Lentis Comfort Toric LS-313 MF15T insertion (Oculentis; Santen Pharmaceutical). In cases of bilateral surgeries, only the right eye was included in the analysis. We also conducted a questionnaire survey about the photic phenomena. RESULTS: The study included 96 eyes from 96 patients. The intermediate-vision zones of 44, 19, 19, and 14 eyes were fixed in the inferior, superior, nasal, and temporal directions, respectively. The measured PPT values for halo, glare, and starburst were equivalent in all the fixed directions. Eighty-four eyes (87.5%) perceived a triangle-shaped halo, and the direction of fixation for the intermediate-vision zone and the extension direction of this photic phenomenon were consistent in 94.0% of the eyes. Less than 10% of the patients responded "moderate" or "severe" for the triangle-shaped halo, glare, and starburst in fixed directions with low frequency in the questionnaire. CONCLUSION: No qualitative or quantitative difference was found in photic phenomena in eyes implanted with the LS-313 MF15 or the MF15T regardless of the fixation direction. Our study revealed that many patients were aware of a triangle-shaped halo extending in the direction of the intermediate-vision zone.

Role of Decorin in the Lens and Ocular Diseases.

Decorin is an archetypal member of the small leucine-rich proteoglycan gene family and is involved in various biological functions and many signaling networks, interacting with extra-cellular matrix (ECM) components, growth factors, and receptor tyrosine kinases. Decorin also modulates the growth factors, cell proliferation, migration, and angiogenesis. It has been reported to be involved in many ischemic and fibrotic eye diseases, such as congenital stromal dystrophy of the cornea, anterior subcapsular fibrosis of the lens, proliferative vitreoretinopathy, et al. Furthermore, recent evidence supports its role in secondary posterior capsule opacification (PCO) after cataract surgery. The expression of decorin mRNA in lens epithelial cells in vitro was found to decrease upon transforming growth factor (TGF)-ß-2 addition and increase upon fibroblast growth factor (FGF)-2 addition. Wound healing of the injured lens in mice transgenic for lens-specific human decorin was promoted by inhibiting myofibroblastic changes. Decorin may be associated with epithelial-mesenchymal transition and PCO development in the lens. Gene therapy and decorin administration have the potential to serve as excellent therapeutic approaches for modifying impaired wound healing, PCO, and other eye diseases related to fibrosis and angiogenesis. In this review, we present findings regarding the roles of decorin in the lens and ocular diseases.

Lens-specific conditional knockout of tropomyosin 1 gene in mice causes abnormal fiber differentiation and lens opacity.

Tropomyosin (Tpm) 1 and 2 are important in the epithelial mesenchymal transition of lens epithelial cells; however, the effect of Tpm1 depletion during aging remains obscure. We analyzed the age-related changes in the crystalline lens of Tpm1- conditional knockout mice (Tpm1-CKO). Floxed alleles of Tpm1 were conditionally deleted in the lens, using Pax6-cre transgenic mice. Lenses of embryonic day (ED) 14, postnatal 1-, 11-, and 48-week-old Tpm1-CKO and wild type mice were dissected to prepare paraffin sections, which subsequently underwent histological and immunohistochemical analysis. Tpm1 and α smooth muscle actin (αSMA) mRNA expression were assessed using RT-PCR. The homozygous Tpm1-CKO (Tpm1-/-) lenses displayed a dramatic reduction in Tpm1 transcript, with no change to αSMA mRNA expression. Tpm1-/- mice had small lenses with disorganized, vesiculated fiber cells, and loss of epithelial cells. The lenses of Tpm1-/- mice had abnormal and disordered lens fiber cells with cortical and peri-nuclear liquefaction. Expression of filamentous-actin was reduced in the equator region of lenses derived from ED14, 1-, 11-, and 48-week-old Tpm1-/- mice. Therefore, Tpm1 plays an integral role in mediating the integrity and fate of lens fiber differentiation and lens homeostasis during aging. Age-related Tpm1 dysregulation or deficiency may induce cataract formation.

Quantitative assessment of photic phenomena in the presbyopia-correcting intraocular lens.

This was a prospective study to evaluate the feasibility of the photic phenomena test (PPT) for quantifying glare, halo, and starburst. We compared two presbyopia-correcting intraocular lenses (IOLs), the Symfony IOL and the PanOptix IOL, as well as the monofocal Clareon IOL in 111 IOL-implanted eyes of 111 patients who underwent the PPT 1 month postoperatively. The reproducibility of photic phenomena with the PPT was assessed in 39 multifocal IOL-implanted eyes of 20 patients and among the examiners. Patients with ocular diseases, except for refractive errors, were excluded. The mean values of the groups were evaluated. Bland-Altman plots were used to analyze statistical data (Easy R version 1.37; R Foundation for Statistical Computing, Vienna, Austria). The PPT reproducibility assessment revealed no fixed bias or regressive significance. Reproducibility was confirmed. The glare size did not differ significantly between the Symfony, PanOptix, and Clareon groups. The halo size was significantly larger in the Symfony group (p < 0.01) than in the PanOptix group. The halo intensity was significantly brighter in the PanOptix group (p < 0.01) than in the Symfony group. In contrast, no halos were perceived in the Clareon group. The starburst size or intensity did not differ significantly between the Symfony, PanOptix, and Clareon groups. We identified the photic phenomenon related to various IOLs.

Association among pterygium, cataracts, and cumulative ocular ultraviolet exposure: A cross-sectional study in Han people in China and Taiwan.

PURPOSE: Pterygium is an ocular surface disorder mainly caused by ultraviolet (UV) light exposure. This study explored the relationships between six cataract types with pterygium and UV exposure. METHODS: We have previously studied cataracts in residents of three regions in China and Taiwan with different UV intensities. From that study, we identified 1,547 subjects with information on the presence or absence of pterygium. Pterygium severity was graded by corneal progress rate. Cataracts were graded by classification systems as three main types (cortical, nuclear, posterior subcapsular) and three subtypes (retrodots, waterclefts, fiber folds) with high prevalence in middle-aged and elderly people. We calculated the cumulative ocular UV exposure (COUV) based on subject data and National Aeronautics and Space Administration data on UV intensities and used logistic regression to calculate odds ratios for the associations of COUV, cataract, and pterygium. RESULTS: We found an overall pterygium prevalence of 23.3%, with significant variation among the three regions. Four cataract types (cortical, nuclear, posterior subcapsular, and retrodots) were significantly associated with the presence of pterygium. CONCLUSIONS: There was a significant association between COUV and pterygium, indicating that COUV is associated with the risk of pterygium development and that pterygium is useful as an index of UV exposure. Furthermore, the type of cataract in eyes with pterygium may indicate the level of UV exposure.

Lutein plus Water Chestnut (Trapa bispinosa Roxb.) Extract Inhibits the Development of Cataracts and Induces Antioxidant Gene Expression in Lens Epithelial Cells.

Age-related cataract (ARC) is the major cause of blindness worldwide. The most significant factors are the maximal exposure of the eye lens to environmental stressors, including oxidative and glycative load. The administration of antioxidant and antiglycative supplements may reduce the risk of cataract progression. In this study, the effects of lutein (LU) and water chestnut (Trapa bispinosa Roxb.) extract (TBE) on cataracts and the expression of antioxidant-related genes were assessed in Shumiya cataract rats (SCRs). LU+TBE or castor oil (COil) as a control was administered to 6- or 9-week-old cataractous SCRs and noncataractous SCRs via a feeding needle for 3 or 4 weeks. Five-week-old SCRs were provided ad libitum access to solid regular chow containing LU, TBE, LU+TBE, or the same chow without LU and/or TBE for 3 weeks. Lenses from all rats were then extracted and photographed. The right eyes of the rats were processed for histological observation, and the left eyes were used for total RNA extraction from lens epithelial cells (LEC). The mRNA levels of antioxidant proteins, peroxiredoxin 6, and catalase were examined using real-time quantitative polymerase chain reaction. Lens opacity appeared in all cataractous SCRs that began receiving LU+TBE at 9 weeks of age. However, compared to the COil group, lens opacity was decreased in the cataractous LU+TBE SCRs in all experiments. The mRNA expression levels of peroxiredoxin 6 and catalase in LECs of cataractous SCRs and cultured human LECs increased after the administration of LU+TBE. Collectively, our results highlight the anticataract and antioxidative effects of LT+TBE in SCRs. LT+TBE supplementation may, thus, be useful in delaying cataract progression.

Degradation of connexin 50 protein causes waterclefts in human lens.

Cataracts are mainly classified into three types: cortical cataracts, nuclear cataracts, and posterior subcapsular cataracts. In addition, retrodots and waterclefts are cataract subtypes that cause decreased visual function. To maintain an orderly and tightly packed arrangement to minimize light scattering, adhesion molecules such as connexins and aquaporin 0 (AQP0) are highly expressed in the lens. We hypothesized that some main and/or subcataract type(s) are correlated with adhesion molecule degradation. Lens samples were collected from cataract patients during cataract surgery, and mRNA and protein expression levels were measured by real-time RT-PCR and western blotting, respectively. The mRNA levels of adhesion molecules were not significantly different among any cataract types. Moreover, AQP0 and connexin 46 protein expressions were unchanged among patients. However, connexin 50 protein level was significantly decreased in the lens of patients with WC cataract subtype. P62 and LC3B proteins were detected in the WC patients' lenses, but not in other patients' lenses. These results suggest that more research is needed on the subtypes of cataracts besides the three major types of cataract for tailor-made cataract therapy.

Enhancement of Amyloid ß1-43 Production in the Lens Epithelium of Japanese Type 2 Diabetic Patients.

We investigated whether the accumulation of amyloid ß-protein (Aß) is enhanced in the lenses of diabetic patients. Lens epithelium samples were collected from Japanese patients during cataract surgery, and the Aß levels and gene expression of Aß-producing and -degrading enzymes in the samples were measured by ELISA and real-time RT-PCR, respectively. The Aß 1-43 levels in lenses of non-diabetic patients were low (0.11 pmol/g protein), while the levels in lenses of diabetic patients were significantly (6-fold) higher. Moreover, the Aß1-43/total-Aß ratio in the lenses of diabetic patients was also significantly higher than non-diabetic patients (p < 0.05). In addition, the mRNA levels for Aß-producing enzymes were also enhanced in the lenses of diabetic patients. In contrast to the results for Aß-producing enzymes, the mRNAs for the Aß-degrading enzymes in the lenses of diabetic patients were significantly lower than in non-diabetic patients (p < 0.05). Furthermore, Aß 1-43/total-Aß ratio in lenses was found to increase with plasma glucose level. In conclusion, these results suggest that high glucose levels cause both an increase in Aß production and a decrease in Aß degradation, and these changes lead to the enhancement in Aß1-43 accumulation in the lenses of diabetic patients. These findings are useful for developing therapies for diabetic cataracts and for developing anti-cataract drugs.

Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat.

The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-thirds of these rats develop lens opacity within 10-11 weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR are poorly understood. In the present study, a microarray-based approach was employed to analyze comparative gene expression changes in LECs isolated from the precataractous and cataractous stages of lenses of 5-week-old SCRs. The changes in gene expression observed in microarray results in the LECs were further validated using real-time reverse transcribed quantitative PCR (RT-qPCR) in 5-, 8-, and 10-week-old SCRs. A mild posterior and cortical opacity was observed in 5-week-old rats. Expressions of approximately 100 genes, including the major intrinsic protein of the lens fiber (Mip and Aquaporin 0), deoxyribonuclease II beta (Dnase2B), heat shock protein B1 (HspB1), and crystallin γ (γCry) B, C, and F, were found to be significantly downregulated (0.07-0.5-fold) in rat LECs derived from cataract lenses compared to that in noncataractous lenses (control). Thus, our study was aimed at identifying the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR. We proposed that cataracts in SCR are associated with reduced expression of these lens genes that have been reported to be related with lens fiber differentiation. Our findings may have wider implications in understanding the effect of cholesterol deficiency and the role of cholesterol-lowering therapeutics on cataractogenesis.

Changes in mitochondrial cytochrome c oxidase mRNA levels with cataract severity in lens epithelia of Japanese patients.

We previously reported that the collapse of ATP production via mitochondrial damage causes ATPase dysfunction, resulting in the onset or progression of lens opacification in cataracts in model rats. In the present study, it was investigated whether the mRNA expression levels of the three subtypes of mitochondrial cytochrome c oxidase (MTCO)1, 2 and 3 and ATP content change with the type and severity of cataracts in human lens. Samples of lens epithelium were collected from Japanese patients during cataract surgery, and the type and severity of the cataracts (grade) were determined according to the WHO classification [cortical (COR), nuclear (NUC), posterior subcapsular (PSC) opacification]. The MTCO1­3 mRNA expression levels in patients with grade­1 COR, NUC and PSC opacification were significantly enhanced compared with those of normal patients. The enhanced MTCO1­3 mRNA levels subsequently decreased in patients with COR, and the MTCO1­3 mRNA levels and ATP levels in patients with grade­3 COR were similar to those in normal patients. However, the mRNA expression levels of MTCO3 in patients with grade 3­NUC opacification and MTCO1­3 in patients with grade­3 PSC opacification, along with the ATP content, were significantly lower than in patients without cataracts. In conclusion, it was revealed that ATP production in lens epithelium is enhanced in early­stage cataracts (grade­1) in Japanese patients with COR, NUC and PSC opacification. In addition, in severe cataracts (grade­3), ATP production and content are strongly decreased in Japanese patients with PSC opacification. ATP depletion in human lens epithelium with PSC opacification may promote lens opacification by ATPase dysfunction.

Visual Function and Functional Decline in Patients With Waterclefts.

Purpose: To investigate visual function in eyes with three subtypes of waterclefts (WCs). Methods: Of patients in Kanazawa Medical University Hospital (2013-2017) and participants of Monzen Eye Study (2013-2016), 77 transparent lenses, mean age 66.7 years, and 70 eyes with only WC opacity of 70 patients, mean age 68.1 years, divided into peripheral-, central-, and total-type WC groups, were analyzed. Opacity was classified by one ophthalmologist using slit-lamp microscopy. Corrected-distance visual acuity (CDVA), contrast visual acuity (CVA), spherical equivalent (SE), astigmatism values, corneal refractive power (CP), axial length (AL), straylight, backward light scattering (BLS), and higher order aberrations (HOA) were measured and lenticular refractive power (LP) was calculated based on the values of AL, CP, and SE. Results: Central-type WC showed significant decrease in CDVA and CVA and increase in straylight compared with control. Total-type WC showed significant decreases in CDVA, CVA, and LP, and increase in straylight, compared with control and peripheral-type WC. Total- and central-type WCs had significantly higher ocular total HOA and total-type WC had significantly higher internal total HOA than control. HOA correlated positively with CDVA (P < 0.001) and straylight (P = 0.020), and CDVA negatively with straylight in eyes with WCs (P = 0.008). Conclusions: Total-type WC was associated with decreased LP, causing hyperopia, decreased CDVA and higher straylight; thus, such lenticular change should be considered for surgery indication. Significant correlations between HOA and both CDVA and straylight suggested increased HOA may decrease visual function in eyes with WCs.

Association between ultraviolet radiation exposure dose and cataract in Han people living in China and Taiwan: A cross-sectional study.

PURPOSE: We investigated associations between ocular ultraviolet (UV) radiation exposure dose and cataract opacities among Han people living in China and Taiwan, to assess the effects of UV exposure intensity. METHODS: This cross-sectional study included Han people aged ≥40 years (1,801 individuals, 450 in Sanya, 636 in Taiyuan, and 715 in Taichung) as subjects who completed a questionnaire including items about diabetes, smoking, steroid use, work history, and time spent outdoors, and underwent an ophthalmic examination. Right eye axial length was measured using A-mode ultrasonography or IOLMaster. Slit-lamp imaging under maximum mydriasis was used to classify cataracts into three major types [cortical (COR), nuclear (NUC), and posterior subcapsular cataracts (PSC)] and two subtypes [retrodots (RD) and waterclefts (WC)] by one ophthalmologist. COR was divided into opacity presence (CEN+) or absence (CEN-) in the central 3-mm diameter area of the pupil. COR was also subdivided into three groups according to opacity shape: axle-shaped opacity concomitant with WC, wedge-shaped opacity around the pupil to the eye center, and ring-shaped opacity in the lens equator along the pupillary margin. The cumulative ocular UV exposure (COUV) was calculated. A logistic regression analysis was used for multivariate analysis. RESULTS: Cataract odds ratios in high COUV eyes were 5.35 for NUC, 1.87 for PSC, and 1.35 for RD. In eyes with WC, risk of COR ring-shaped opacity significantly increased but that of wedge-shaped opacity (CEN+) significantly decreased. In eyes without WC, risk of COR axle-shaped opacity (CEN-) and ring-shaped opacity significantly increased but that of wedge-shaped opacity (CEN+) significantly decreased. CONCLUSIONS: Increased COUV level among Han people may be a risk factor for the development of nuclear cataracts, PSC, retrodots and ring-shaped cortical cataract. Risk of ocular UV exposure for cortical cataract may differ by opacity shape.

Correction: Association between ultraviolet radiation exposure dose and cataract in Han people living in China and Taiwan: A cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0215338.].

Distribution of corneal spherical aberration in a Tanzanian population.

PURPOSE: To investigate the distribution of corneal spherical aberration (SA) in Tanzanian people of African descent, and to examine the correlation between corneal SA and ocular parameters. DESIGN: Cross-sectional population-based study. METHODS: Residents aged 40 years and older in three villages in the Mkuranga district in Tanzania were enlisted as study participants. Corneal higher-order aberrations (HOAs) for the right eye were measured with a wavefront analyzer (KR-1W, Topcon) and calculated for the central 6.0-mm zone. Corneal curvature radius (CR), corneal astigmatism, and axial length (AL) were also measured and their correlation with corneal SA was assessed. RESULTS: The right eyes of 657 participants (336 male, 321 female) were analyzed. The mean age of the subjects was 57.2 ± 10.3 years (mean ± SD). The mean corneal SA (Zernike spherical aberration coefficient C40) was 0.188 ± 0.095 µm (-0.242 to 0.613). The SAs in about three-quarters of all subjects were between 0.10 and 0.30 µm. The root mean squares of total corneal HOAs and the third- and fourth-order aberrations were 0.629 ± 0.250 µm, 0.539 ± 0.236 µm, and 0.269 ± 0.110 µm, respectively. Corneal SA showed weak significant correlations with CR (Spearman's rank correlation coefficient, r = -0.177, p < 0.001), corneal astigmatism (r = -0.142, p < 0.001), AL (r = -0.168, p < 0.001), and age (r = -0.085, p < 0.05). CONCLUSIONS: This finding may be beneficial for selecting aspheric intraocular lens in this population.

Tropomyosin 2 heterozygous knockout in mice using CRISPR-Cas9 system displays the inhibition of injury-induced epithelial-mesenchymal transition, and lens opacity.

The process of epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) after cataract surgery contributes to tissue fibrosis, wound healing and lens regeneration via a mechanism not yet fully understood. Here, we show that tropomyosin 2 (Tpm2) plays a critical role in wound healing and lens aging. Posterior capsular opacification (PCO) after lens extraction surgery was accompanied by elevated expression of Tpm2. Tpm2 heterozygous knockout mice, generated via the clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system showed promoted progression of cataract with age. Further, injury-induced EMT of the mouse lens epithelium, as evaluated histologically and by the expression patterns of Tpm1 and Tpm2, was attenuated in the absence of Tpm2. In conclusion, Tpm2 may be important in maintaining lens physiology and morphology. However, Tpm2 is involved in the progression of EMT during the wound healing process of mouse LECs, suggesting that inhibition of Tpm2 may suppress PCO.

A positive feedback loop between nitric oxide and amyloid ß (1-42) accelerates mitochondrial damage in human lens epithelial cells.

We have reported that excessive nitric oxide (NO), like other reactive oxygen species (ROS), causes a decrease in cytochrome c oxidase (CCO) activity and ATP levels (mitochondrial damage) resulting in lens opacity. In addition, previous reports have shown that oxidative stress caused by ROS enhances amyloid ß (Aß) production in mammalian lenses, and that Aß1-42 stimulates inducible nitric oxide synthase (iNOS) promoter activity. Based on these reports, we investigated the relationship between NO and Aß1-42 production in human lens epithelial (HLE) cells. iNOS was induced by the co-incubation of HLE cells with 1000 IU interferon-γ (IFN-γ) and 100ng/ml lipopolysaccharide (LPS) for 48h. This led to enhanced NO release, an increase in the gene expression levels of proteins related to Aß production, and the cellular accumulation of Aß1-42. Moreover, both aminoguanidine (AG, a selective inhibitor of iNOS) and diethyldithiocarbamate (DDC, a nuclear factor-kappa B (NFκB) inhibitor) attenuated these changes in IFN-γ and LPS stimulated HLE cells. Based on our finding that Aß1-42 accumulation is induced by co-incubation of HLE cells with both IFN-γ and LPS, we prepared a HLE cell model with Aß1-42 accumulation (Aß-accumulated-HLE cell model) by pre-stimulating cells with IFN-γ and LPS for 48h. Aß1-42 accumulation caused NO production via iNOS, resulting in an enhancement in the mRNA levels for enzymes necessary for the proteolysis of amyloid precursor protein (APP) to Aß in HLE cells. In addition, excessive NO produced in response to Aß1-42 accumulation led to a decrease in CCO activity and ATP levels. Taken together, we hypothesize that excessive NO production in the lens epithelium enhances Aß1-42 production, and that this enhancement accelerates NO release. The enhancement in NO production in the lens epithelium based on positive feedback (NO-Aß positive feedback loop, a vicious cycle) may promote the onset of cataracts (lens opacification) via the decrease in CCO activity and ATP levels. These findings provide significant information that can be used to design further studies aimed at developing anti-cataract drugs.