Clinical significance of CTGF and Cry61 protein in extraocular muscles of strabismic patients.

PURPOSE: To investigate the relationship between clinical features and protein amounts of Cysteine-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2), which are vital components and regulators of the extracellular matrix in resected muscles from strabismus surgery. METHODS: Strabismus patients who were diagnosed with horizontal concomitant strabismus or inferior oblique overaction (IOOA) and required extraocular muscles (EOMs) resection to correct eye position were included in this study. The protein amounts were measured by enzyme-linked immunosorbent assay (ELISA) in resected EOMs. Multivariable linear regression was used to investigate the associations, adjusting for gender, age (continuous), amblyopia, and disease duration. RESULTS: A total of 141 muscles (including 38 lateral, 81 medial rectus, and 22 inferior oblique muscles) from 128 patients were collected in this study. The amount of Cry61 and CTGF per millimeter was significantly negatively associated with deviation angle in intermittent exotropia patients (Cry61: ß, - 1.44; 95%CI, - 2.79 to - 0.10, p = 0.035; CTGF: ß, - 3.14; 95%CI, - 5.06 to - 1.22, p = 0.002). The same relationship was also detected in the partially accommodative and non-accommodative esotropia patients, although it was not statistically significant (Cry61: ß, - 2.40; 95%CI, - 5.05 to 0.24; p = 0.073; CTGF: ß, - 3.47; 95%CI, - 9.18 to 2.87; p = 0.269). The amount of Cry61 and CTGF per millimeter showed significant associations with the degree of IOOA (p < 0.05). CONCLUSIONS: Taken together, our results demonstrated a significant relationship between deviation angle and protein amount of Cry61 and CTGF and implied that Cry61 and CTGF may play important roles in modulation of EOM contractility, which provide new insights into strabismus pathogenesis.

Socioeconomic disparities in the global burden of glaucoma: an analysis of trends from 1990 to 2016.

PURPOSE: To assess the global burden of glaucoma by year, age, sex, regions, socioeconomic development, and mean years of schooling (MYS) by using disability-adjusted life year (DALY), then to explore the health inequality with socioeconomic status in glaucoma. METHODS: Global, national, and regional DALY data of glaucoma by year, age, and sex were extracted from the Global Health Data Exchange. Human development index (HDI) and national MYS in 2015 were obtained from the Human Development Report (HDR) 2016. Mann-Whitney U test was performed to explore the sexual difference in global DALYs. Kruskal-Wallis tests were performed to explore the difference of age-standardized DALY rates across WHO regions and HDI-related country groups. Linear regression analyses were performed to explore the association between age-standardized DALY rates with HDI and MYS. Health-related Gini coefficients and concentration indexes were calculated to evaluate the trends in health inequality of glaucoma since 1990. RESULTS: DALY numbers, crude DALY rates, and age-standardized DALY rates increased by 118.0%, 55.22%, and 12.12%, respectively, since 1990. Global DALY numbers and crude DALY rates increased with age, and Mann-Whitney U test revealed no significant sex difference in global DALY numbers (P = 0.807) and global crude DALYs rates (P = 0.976) for each age group in 2016. Africa and Eastern Mediterranean had higher age-standardized DALY rates than the global one in 2016. Kruskal-Wallis test indicated significant difference in age-standardized DALY rates across WHO regions (χ2 = 94.227, P < 0.001). Linear regression analysis indicated that HDI (adjusted R2 = 0.079; F = 16.722, P < 0.001) and MYS (adjusted R2 = 0.108; F = 23.048, P < 0.001) had a significant effect on age-standardized DALY rates. Gini coefficients rose from 0.290 in 1990 to 0.292 in 2015 with a peak value 0.299 in 2005, concentration index declined from 1990 (- 0.099) to 2000 (- 0.077) with reaching a low peak value, then rapidly increased to - 0.097 in 2015. CONCLUSIONS: With population growth and aging, global burden of glaucoma is increasing and older age, lower socioeconomic status, and lower MYS are associated with higher glaucoma burden. Our results help to gain a better understanding of glaucoma and guide future health policies tailored for public.

Regional differences in the global burden of age-related macular degeneration.

BACKGROUND: Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making. METHODS: Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn's multiple comparisons test as well as regression analysis. RESULTS: Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years. CONCLUSIONS: The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.

Scanning and transmission electron microscopy study of anterior lens epithelium in presenile cataract.

PURPOSE: To study the structure of lens epithelial cells (LECs) in the anterior lens epithelium of presenile cataract and to further explore the possible reasons for presenile cataract development. METHODS: The anterior lens capsules (aLCs) of patients with presenile cataracts and patients with ordinary age-related cataracts were obtained from routine cataract surgery, and the 5-5.5 mm circles of the central aLC were cut in half and prepared for transmission electron microscopy (TEM) and scanning electron microscopy (SEM). RESULTS: The most obvious structural changes in the LECs observed in both cataract groups by TEM were uneven thickness of the anterior lens epithelium, vacuolated cytoplasm and elongated nuclei. SEM showed abnormal structural changes in the LECs, with swollen cells and spheres on the anterior lens epithelium observed in both groups and holes formed by the LECs stretching observed only in the presenile cataract patients. The degeneration of the anterior lens epithelium and the structural changes in the LECs were observed more prominently in presenile cataract patients. CONCLUSIONS: Abnormal and prominently affected structural features of LECs were observed in the presenile compared to age-related cataract patients by TEM and SEM. We suppose that ultrastructural pathological changes in the anterior lens epithelial cells are one of the important reasons for the development of presenile and age-related cataract.

The impact of GJA8 SNPs on susceptibility to age-related cataract.

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for general ARC under both recessive and additive models; and rs6657114 for cortical cataract under the recessive model. To uncover the underlying mechanisms, this study also sought to explore whether GJA8 is involved in the autophagy process in human lens epithelial cells. The results showed that GJA8 may participate in autophagy to maintain the intracellular environment, which may be a novel mechanism for cataract formation induced by GJA8. In conclusion, this study identified the genetic susceptibility of GJA8 polymorphisms on ARC and provides new clues for fully understanding the pathological mechanism of GJA8 variants in affecting lens opacity.

Identification of seven novel ZNF469 mutations in keratoconus patients in a Han Chinese population.

PURPOSE: To test for the potential presence of novel mutations in the zinc finger protein (ZNF469) gene in patients with sporadic keratoconus (KC) from a Han Chinese population. METHODS: Fifty-three patients with primary KC, 30 patients with high myopia (HM), and 100 unrelated population-matched healthy controls without any ocular or systemic disorders, all of Han Chinese ethnicity, were recruited. Blood samples were donated, and genomic DNA was isolated from peripheral blood leukocytes. Sequence variations in ZNF469 were initially identified in patients with KC with next-generation sequencing and subsequently confirmed using Sanger sequencing. Sequence variants identified in patients with KC were subsequently screened in 30 patients with HM and 100 healthy control subjects. Other genes that were reported to be related to KC were also screened in the patients with KC who carried the mutations in ZNF469. The Sorting Intolerant Form Tolerant (SIFT) program was used to predict the effect of amino acid substitution on the ZNF469 protein. RESULTS: Sixteen sequence variants in the coding regions of ZNF469 were identified in this Chinese KC cohort. After five known single nucleotide polymorphisms (SNPs), one false-positive result, and three mutations that were also detected in the results of the whole-exome sequencing (WES) data performed in 220 Han Chinese individuals without ocular abnormalities were removed, seven novel mutations in ZNF469 (c.2059G>A, c.2137C>A, c.3466G>A, c.3749C>T, c.4300G>A, c.4684G>A, and c.7262G>A) that were predicted to be potentially damaging were identified. The patient with KC with the c.3466G>A mutation was also shown to carry one dedicator of cytokinesis 9 (DOCK9) mutation (c.1940C>T). None of the mutations were detected in the patients with HM or the healthy controls. All of the seven mutations in the patients with KC were heterozygote. CONCLUSIONS: The results suggested for the first time that ZNF469 has a pathogenic role in Chinese patients with KC and have widened the mutation spectrum of KC in the Han Chinese population.

Targeted dexamethasone nano-prodrug for corneal neovascularization management.

BACKGROUND: To overcome the drawbacks of traditional therapy for corneal neovascularization (CNV), we evaluated the efficacy of polyethylene glycol (PEG)-conjugated Ala-Pro-Arg-Pro-Gly (APRPG) peptide modified dexamethasone (Dex), a novel nano-prodrug (Dex-PEG-APRPG, DPA). METHODS: Characterization of DPA nano-prodrug were measured with transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses. Cytotoxicity and effects on cell migration and tube formation of DPA were evaluated in vitro. A murine CNV model was established by cornea alkali burn. The injured corneas were given eye drops of DPA (0.2 mM), Dex solution (0.2 mM), Dexp (2 mM), or normal saline three times a day. After two weeks, eyes were obtained for the analysis of histopathology, immunostaining, and mRNA expression. RESULTS: DPA with an average diameter of 30 nm, presented little cytotoxicity and had good ocular biocompatibility. More importantly, DPA showed specific targeting to vascular endothelial cells with efficient inhibition on cell migration and tube formation. In a mouse CNV model, clinical, histological, and immunohistochemical examination results revealed DPA had a much stronger angiogenesis suppression than Dex, resembling a clinical drug with an order of magnitude higher concentration. This was ascribed to the significant downregulations in the expression of pro-angiogenic and pro-inflammatory factors in the corneas. In vivo imaging results also demonstrated that APRPG could prolong ocular retention time. CONCLUSIONS: This study suggests that DPA nano-prodrug occupies advantages of specific targeting ability and improved bioavailability over conventional therapy, and holds great potential for safe and efficient CNV therapy.

Lens autophagy protein ATG16L1: a potential target for cataract treatment.

Rationale: Cataract is the leading cause of blindness and low vision worldwide, yet its pathological mechanism is not fully understood. Although macroautophagy/autophagy is recognized as essential for lens homeostasis and has shown potential in alleviating cataracts, its precise mechanism remains unclear. Uncovering the molecular details of autophagy in the lens could provide targeted therapeutic interventions alongside surgery. Methods: We monitored autophagic activities in the lens and identified the key autophagy protein ATG16L1 by immunofluorescence staining, Western blotting, and transmission electron microscopy. The regulatory mechanism of ATG16L1 ubiquitination was analyzed by co-immunoprecipitation and Western blotting. We used the crystal structure of E3 ligase gigaxonin and conducted the docking screening of a chemical library. The effect of the identified compound riboflavin was tested in vitro in cells and in vivo animal models. Results: We used HLE cells and connexin 50 (cx50)-deficient cataract zebrafish model and confirmed that ATG16L1 was crucial for lens autophagy. Stabilizing ATG16L1 by attenuating its ubiquitination-dependent degradation could promote autophagy activity and relieve cataract phenotype in cx50-deficient zebrafish. Mechanistically, the interaction between E3 ligase gigaxonin and ATG16L1 was weakened during this process. Leveraging these mechanisms, we identified riboflavin, an E3 ubiquitin ligase-targeting drug, which suppressed ATG16L1 ubiquitination, promoted autophagy, and ultimately alleviated the cataract phenotype in autophagy-related models. Conclusions: Our study identified an unrecognized mechanism of cataractogenesis involving ATG16L1 ubiquitination in autophagy regulation, offering new insights for treating cataracts.

Incidence and analysis of intraoperative complications in femtosecond laser-assisted cataract surgery: a large-scale cohort study to establish the learning curve.

AIMS: To assess the safety of femtosecond laser-assisted cataract surgery (FLACS) based on surgical parameters and intraoperative complications analysis and to determine the length of the learning curve for FLACS. METHODS: A prospective consecutive cohort study was conducted on Chinese patients who underwent either FLACS (3289 cases) or contemporaneous conventional phacoemulsification cataract surgery (2130 cases). The laser group was divided into four subgroups in chronological order. We recorded intraoperative complication incidences and compared with surgical parameters between groups. Subgroup analysis was conducted to explore the learning curve of FLACS. RESULTS: The laser group had a 4.93% incidence of incomplete capsulotomies and a 1.22% incidence of anterior capsule tears. Subgroup analysis showed significant differences in 8 aspects between the first 250 cases (50 cases per surgeon) and the last 2539 cases, but only 2 aspects differed between the second 250 cases (50 cases per surgeon) and the last 2539 cases. There were no significant differences between the third 250 cases (50 cases per surgeon) and the last 2539 cases. CONCLUSIONS: The intraoperative complications of FLACS were reported, and the learning curve is associated with a significant reduction in the incidence of intraoperative complications. The length of the basic learning curve of FLACS is 100 cases, and the length of the advanced learning curve was 150 cases. This study demonstrated that FLACS is characterised by a relatively straightforward and secure operative technique.

Bromfenac sodium 0.1%, fluorometholone 0.1% and dexamethasone 0.1% for control of ocular inflammation and prevention of cystoid macular edema after phacoemulsification.

PURPOSE: To compare bromfenac sodium 0.1%, fluorometholone 0.1% and dexamethasone 0.1% for the control of postoperative inflammation and prevention of cystoid macular edema (CME) after phacoemulsification. METHODS: Patients were randomized to receive bromfenac sodium 0.1% for 1 month (OBS1) or 2 months (OBS2), or fluorometholone 0.1% for 1 month (OFM) or dexamethasone 0.1% for 1 month (ODM). Best-corrected visual acuity, intraocular pressure, endothelial cell density, photon count value and retinal foveal thickness were measured. RESULTS: Mean photon count values were lower in the OBS1 and OBS2 groups compared with the ODM group during the first week. Bromfenac sodium cleared the ocular inflammation more rapidly than fluorometholone and dexamethasone. The foveal thickness was thinner in the second month and the incidence of CME was lower in the OBS1 and OBS2 groups compared with the OFM and ODM groups. CONCLUSION: Bromfenac sodium was more effective and safer than fluorometholone and dexamethasone as an anti-inflammatory, decreasing macular thickness and preventing CME in age-related cataract patients after cataract surgery.

[Study of the visual deficits pattern in strabismic and anisometropic amblyopia].

OBJECTIVE: To elucidate the difference in the pathogenesis between strabismic and anisometropic amblyopia. METHODS: It was a case-control study.We used psychophysical methods, including grating acuity, edge contrast sensitivity, contrast sensitivity function tests, and examined the visual functions of 150 cases from 8 to 40-year-old. Then we applied the Origin 8.0 software for statistical analysis of experimental data, we did the correlation analysis between the grating acuity, edge contrast sensitivity and optotype acuity, and the similarity comparison of the contrast sensitivity function curve between the strabismic and anisometropic amblyopia. RESULTS: The grating acuity had a strong correlation with optotype acuity, the correlation value was 0.81. The grating acuity of the strabismic group was roughly 15% lower than the whole abnormal population, for any given level of optotype acuity; the edge contrast threshold had a weak correlation with optotype acuity, the correlation value was 0.24. Anisometropia, for a given level of optotype acuity, had edge contrast thresholds that were 15% higher (worse) than the whole population, while strabismic and strabismic-anisometropia had edge contrast thresholds that are 17% lower (better) than the whole population. The CSF of all amblyopic eyes were reduced in comparison with the non-amblyopic eye of the same person, the peak sensitivity shifted toward to the low spatial frequency region, the CS curve was depressed especially in the middle and high spatial frequencies, there were no significant difference, but at low frequency area(1.0 c/d) there were statistically significant between the two types of amblyopia(t = 2.239, P < 0.05). CONCLUSION: There were differences in the patterns of visual loss between strabismic and anisometropic amblyopic patients.

Znf469 Plays a Critical Role in Regulating Synthesis of ECM: A Zebrafish Model of Brittle Cornea Syndrome.

Purpose: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder characterized by extreme thinning and fragility of the cornea, and mutations in ZNF469 cause BCS-1. We aimed to establish a znf469 mutant zebrafish line to explore its roles and possible pathogenic mechanism in cornea development and disorder. Methods: znf4694del/4del mutant zebrafish was generated using the CRISPR/Cas9 technology. Transmission electron microscopy (TEM) was performed to examine the phenotype of the cornea in different developmental stages. RNA sequencing and quantitative real-time polymerase chain reaction were used to reveal the molecular mechanism. Results: Macroscopically, homozygous znf469 mutant zebrafish larvae exhibited a curved body from 72 hours postfertilization, similar to kyphoscoliosis, and a noninflated swimbladder at 7 days postfertilization (dpf). TEM revealed an extreme reduction of corneal stroma thickness in homozygous znf469 mutant zebrafish in both the central and peripheral cornea from the early development stage. RNA-sequencing analysis demonstrated that the znf469 mutation leads to the decreased synthesis of various extracellular matrix (ECM) components, such as collagens and proteoglycans, but increased synthesis of 26S proteasome family members. Conclusions: The results of our work indicate that znf469 is a critical gene that, as a widely considered transcription factor, may regulate the synthesis and degradation of a large number of ECM components that play an important role in corneal development.

Role of Rapamycin and 3-MA in oxidative damage of HLECs caused by two doses of UVB radiation.

Background: This study compared the role of autophagy regulators Rapamycin and 3-MA in oxidative damage and apoptosis of human lens epithelial cells (HLECs) caused by two doses of Ultraviolet Radiation B (UVB). Methods: HLECs were irradiated with UVB, and two doses of UVB damage models were constructed. After treatment with autophagy regulators, cell damage tests such as CCK-8, LDH activity, and Ros detection were performed. Western blotting was used to detect the levels of autophagy-related proteins and apoptosis-related proteins. Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA leve of secondary antioxidant enzymes.Flow cytometry was used to examine cell viability and apoptosis. Finally, the proportion of autophagy and apoptosis was observed by electron microscope. Results: Autophagy inhibitor 3-MA promoted oxidative damage and apoptosis of HLECs at low doses of UVB (5 mJ/cm2), which corresponds to 1.3 â€‹h of exposure to sunlight in human eyes. Under the high dose of UVB (50mJ/cm2), which is equivalent to 13 â€‹h of exposure to sunlight in human eyes, the autophagy inducer Rapamycin caused more extensive oxidative damage and apoptosis of HLECs. 3-MA was able to reduce this damage, indicating that moderate autophagy is necessary for HLECs to cope with mild oxidative stress. For high dose UVB-induced oxidative stress, the use of 3-MA inhibiting autophagy is more beneficial to reduce cell damage and apoptosis. The mechanisms include degradation of damaged organelles, regulation of the expression of antioxidant enzymes HO-1, NQO1, GCS and regulation of apoptosis-related proteins. Conclusions: Autophagy played different roles in HLECs oxidative stress induced by two doses of UVB. It provides new ideas for reducing oxidative damage and apoptosis of HLECs to prevent or delay the progression of age-related cataract (ARC).

Glycolysis Aids in Human Lens Epithelial Cells' Adaptation to Hypoxia.

Hypoxic environments are known to trigger pathological damage in multiple cellular subtypes. Interestingly, the lens is a naturally hypoxic tissue, with glycolysis serving as its main source of energy. Hypoxia is essential for maintaining the long-term transparency of the lens in addition to avoiding nuclear cataracts. Herein, we explore the complex mechanisms by which lens epithelial cells adapt to hypoxic conditions while maintaining their normal growth and metabolic activity. Our data show that the glycolysis pathway is significantly upregulated during human lens epithelial (HLE) cells exposure to hypoxia. The inhibition of glycolysis under hypoxic conditions incited endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production in HLE cells, leading to cellular apoptosis. After ATP was replenished, the damage to the cells was not completely recovered, and ER stress, ROS production, and cell apoptosis still occurred. These results suggest that glycolysis not only performs energy metabolism in the process of HLE cells adapting to hypoxia, but also helps them continuously resist cell apoptosis caused by ER stress and ROS production. Furthermore, our proteomic atlas provides possible rescue mechanisms for cellular damage caused by hypoxia.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens.

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property, which provided a promising approach for PCO prophylaxis in clinical application.

Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by ßB2-G149V Mutation.

Congenital cataracts account for approximately 5-20% of childhood blindness worldwide and 22-30% of childhood blindness in developing countries. Genetic disorders are the primary cause of congenital cataracts. In this work, we investigated the underlying molecular mechanism of G149V point missense mutation in ßB2-crystallin, which was first identified in a three-generation Chinese family with two affected members diagnosed with congenital cataracts. Spectroscopic experiments were performed to determine the structural differences between the wild type (WT) and the G149V mutant of ßB2-crystallin. The results showed that the G149V mutation significantly changed the secondary and tertiary structure of ßB2-crystallin. The polarity of the tryptophan microenvironment and the hydrophobicity of the mutant protein increased. The G149V mutation made the protein structure loose and the interaction between oligomers was reduced, which decreased the stability of the protein. Furthermore, we compared ßB2-crystallin WT and the G149V mutant with their biophysical properties under environmental stress. We found that the G149V mutation makes ßB2-crystallin more sensitive to environmental stresses (oxidative stress, UV irradiation, and heat shock) and more likely to aggregate and form precipitation. These features might be important to the pathogenesis of ßB2-crystallin G149V mutant related to congenital cataracts.

A recurrent PAX6 mutation is associated with aniridia and congenital progressive cataract in a Chinese family.

PURPOSE: Aniridia is phenotyically and genetically heterogeneous. This study is to summarize the phenotypes and identify the genetic defect responsible for aniridia and congenital progressive cataract in a three generation Chinese family. METHODS: A detailed family history and clinical data from patients were collected by ophthalmologic examination, including visual acuity, slit-lamp examination, tonometer, keratometry, corneal topography, optical coherence tomography, and ultrasonic A/B scan. All exons and flanking intronic sequences of the paired box 6 (PAX6) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structure and function of the mutant PAX6 were analyzed by bioinformatics analysis. RESULTS: All the six patients shared common manifestations of complete aniridia, congenital cataract and thickened cornea, and broad phenotypic variability was observed in nystagmus, ptosis, strabismus, glaucoma, corneal pannus, corneal curvature, corneal vascularization, cataract subtype, ectopia lentis, axial length, and optic disc anomalies. Sequencing of the candidate gene detected a heterozygous c.307C>T transition in the coding region of PAX6, resulting in the substitution of a highly conserved arginine codon for a termination codon (p.R103X). The p.P103X mutation co-segregated with the affected individuals in the family. The change was supposed to cause structural and functional changes based on computational analysis. CONCLUSIONS: We identified a recurrent PAX6 c.307C>T mutation in an aniridia and congenital progressive cataract family, and summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of aniridia in a different ethnic background.

[Would micro-incision phacoemulsification be a new trend of cataract surgery].

Coaxial small-incision phacoemulsification has become the most performed and widely accepted cataract surgery in the world. With the development of phaco technique and advances in surgery skills, ophthalmologists pay more and more attention to micro-incision phacoemulsification. Clinically, there are a number of debates focusing on efficiency and safety of micro-incision phacoemulsification. By analyzing the clinical and laboratory studies at home and abroad, we believe that micro-incision phacoemulsification is safe, efficient and economic. Therefore, it will be a new trend of cataract surgery. In order to support our view and to improve ophthalmologists' understanding about micro-incision phacoemulsification and ultimately strengthen their clinical performance, we primarily introduce the history, features and effects of micro-incision phacoemulsification in this paper.

Circulating fatty acids and risk of primary open-angle glaucoma: A mendelian randomization study.

PURPOSE: The relationship between fatty acids (FAs) and glaucoma remains controversial despite several observational studies. We organized a mendelian randomization (MR) study to determine the genetic causal association between circulating FAs and primary open-angle glaucoma (POAG). METHODS: The two-sample MR method was used to acquire causal estimates. Fourteen distinct single nucleotide polymorphisms (SNPs) of ten FAs were chosen as instrumental variables (IVs) at a genome-wide significance level (p < 5 × 10-8). Summary statistics for POAG were available from a genome-wide association meta-analysis of 216,257 individuals of European ancestry (16,677 cases, 199,580 controls). The inverse-variance weighted (IVW) method was adopted to evaluate the causality of FAs and POAG. Multiple sensitivity analyses were applied to avoid pleiotropy. RESULTS: The IVW method suggested no evidence to support causal effects of ten FAs on POAG. The odds ratio (OR) per one SD increment of each FA was ORALA = 1.64 (95% CI, 0.441-6.098, p = 0.46), OREPA = 0.815 (95% CI, 0.604-1.101, p = 0.182), ORDPA = 0.896 (95% CI, 0.669-1.198, p = 0.458), ORDHA = 1.014 (95% CI, 0.801-1.283, p = 0.91), ORLA = 1.008 (95% CI, 0.971-1.045, p = 0.683), ORAA = 0.993 (95% CI, 0.973-1.013, p = 0.483), ORPOA = 0.731 (95% CI, 0.261-2.048, p = 0.551), OROA = 1.048 (95% CI, 0.934-1.175, p = 0.425), ORPA = 1.039 (95% CI, 0.903-1.196, p = 0.593), ORSA = 0.967 (95% CI, 0.879-1.062, p = 0.477). Moreover, Sensitivity analysis indicated no pleiotropy. CONCLUSION: This MR study does not support causal associations between ten FAs and POAG.

Necroptosis contributes to airborne particulate matter-induced ocular surface injury.

In this study, we explored the role of necroptosis in the pathogenesis of ocular surface injury caused by airborne particulate matter (PM). Human corneal epithelial (HCE) cells and mouse ocular surface were treated with PM exposure and compared with non-exposed groups. The expression of necroptosis-related proteins was measured by immunoblotting in HCE cell groups. Cell damages were detected using CCK-8, flow cytometry, and immunofluorescence staining. In the mouse model, hematoxylin and eosin (H&E) staining and corneal fluorescein sodium staining were assessed. In addition, the expression of inflammatory cytokines and mucin were examined via Enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and/or quantitative RT -PCR (qRT-PCR), both in vitro and in vivo. Our research showed that PM exposure may trigger HCE cell damage via necroptosis. Necrostatin-1(Nec-1), one of the specific inhibitors of necroptosis, can markedly reduce PM-induced HCE cell damage. HCE cell damage markers included decreased cell viability, increased intracellular reactive oxygen species (ROS) levels, and loss of mitochondrial membrane potential. At the same time, Nec-1 inhibited the increased inflammatory cytokines and the decreased mucin expression caused by PM exposure in HCE cells. Nec-1 also reduced corneal inflammation and mucin underproduction in mouse ocular surface after PM exposure. Our study demonstrated that necroptosis is involved in the pathogenesis of PM exposure-related ocular surface injury, including inflammation and insufficient mucin production in the cornea, which can be rescued by inhibitor Nec-1. This suggests Nec-1 could be a novel therapeutic target for ocular surface disorders, especially dry eye disease, which is caused by the exacerbation of airborne PM pollution.