Cataract-causing Y204X mutation of crystallin protein CRYßB1 promotes its C-terminal degradation and higher-order oligomerization.

Crystallin proteins are a class of main structural proteins of the vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode these crystallin proteins is the most common cause for congenital cataracts. Despite extensive studies, the pathogenic and molecular mechanisms that effect congenital cataracts remain unclear. In this study, we identified a novel mutation in CRYBB1 from a congenital cataract family, and demonstrated that this mutation led to an early termination of mRNA translation, resulting in a 49-residue C-terminally truncated CRYßB1 protein. We show this mutant is susceptible to proteolysis, which allowed us to determine a 1.2-Å resolution crystal structure of CRYßB1 without the entire C-terminal domain. In this crystal lattice, we observed that two N-terminal domain monomers form a dimer that structurally resembles the WT monomer, but with different surface characteristics. Biochemical analyses and cell-based data also suggested that this mutant is significantly more liable to aggregate and degrade compared to WT CRYßB1. Taken together, our results provide an insight into the mechanism regarding how a mutant crystalin contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in protein aggregation.

The association of demodex infestation with pediatric chalazia.

PURPOSE: This study aimed to investigate the association of Demodex infestation with pediatric chalazia. METHODS: In a prospective study, 446 children with chalazia and 50 children with non-inflammatory eye disease (controls) who underwent surgical treatment were enrolled from December 2018 to December 2019. Patient ages ranged from 7 months to 13 years old. All patients underwent eyelash sampling for light microscope examination, and statistical correlation analysis between Demodex infestation and chalazia, including the occurrence, recurrence, and course of disease, morphological characteristics, and meibomian gland dysfunction (MGD) in chalazia patients was performed. RESULTS: Demodex was found in 236 (52.91%) patients with chalazia and zero control patients. Demodicosis was significantly more prevalent in chalazia patients than the control group (P < 1 × 10- 14). Recurrent chalazia (P = 0.006) and skin surface involvement (P = 0.029) were highly correlated with Demodex infestation. Demodicosis was also associated with multiple chalazia (P = .023) and MGD(P = .024). However, Demodex infestation was comparable in the course of disease (P = 0.15), seasonal change (P = 0.68) and blepharitis subgroups (P = 0.15). Within the group of chalazia patients who underwent surgical removal of cysts, 4 (0.9%) patients with concurrent demodicosis experienced recurrence. CONCLUSIONS: Demodex infestation was more prevalent in pediatric chalazia patients than healthy children, and was associated with recurrent and multiple chalazia. Demodicosis should be considered as a risk factor of chalazia. In children with chalazia, Demodex examination and comprehensive treatment of Demodex mites should be applied to potentially prevent recurrence.

Establishing a novel lens opacities classification system based on ultrasound biomicroscopy (UBM) for pediatric cataracts: reliability and availability.

BACKGROUND: This study sought to develop and validate a lens opacities classification system based on ultrasound biomicroscopy (UBM) imaging to grade pediatric cataracts. METHODS: The study was conducted at Guangzhou Children's Hospital, Guangzhou Women and Children's Medical Center. UBM images of patients at the hospital from September 2013 to November 2014 were used in this study. We summarized the characteristics of lenticular opacification in each of the following 4 zones: the anterior capsule (A); the cortex (C); the nucleus (N); and the posterior capsule (P). The UBM data and intraoperative videos were compared, and sensitivity, specificity, accuracy, and positive and negative predictive values were determined for our Lens Opacities Classification System based on UBM for Pediatric Cataracts (LOCS-UP) detection. Two physicians classified pediatric cataracts (anterior capsule, cortex, and posterior capsule) by extracting 146 images from the UBM database. Patients' data were recorded to calculate the kappa coefficients. The LOCS-UP was developed. RESULTS: Under this standard, all types of pediatric cataracts can be classified and acquired a code by the LOCS-UP. The LOCS-UP had the highest sensitivity (100%) and specificity (98.96%) in naming the anterior capsule and the lowest sensitivity (50%) and specificity (89.59%) in naming the posterior capsule. Its consistency at naming the anterior capsule was satisfactory (Kappa coefficient: 0.70), and it was also able to name the nucleus, cortex, and posterior capsule (0.56, 0.58, and 0.48, respectively). CONCLUSIONS: LOCS-UP could name pediatric cataracts by providing an unique digital encoding, which could reflect characteristics exactly for different local lens anomalies to all kinds of pediatric cataract patients. This method provides detailed and accurate information about Patients' lenses.

Ultrasound Biomicroscopy Detects Peters' Anomaly and Rieger's Anomaly in Infants.

AIM: Congenital corneal opacities (CCOs) are the major causes of early visual deprivation in infants. Balloon ultrasound biomicroscopy (UBM) examination is an effective method to diagnose CCO. However, whether it is suitable for children examination is still unknown. METHODS: 26 Peters' anomaly (PA) or Rieger's anomaly (RA) infants with congenital corneal opacities (CCO) (40 eyes) underwent UBM examinations to study their imaging features. RESULTS: Based on the results, they were divided into UBM Dx-Type I: Descemet's membrane (DM) and endothelium have heterogenous or discontinuous echo accompanied with corneal stroma echo-enhanced or shallow anterior chamber. Type II: Type I alteration plus abnormal strand of iris extended to the border of the posterior corneal defect or iridocorneal adhesion. Type III: Type I or II combined with the abnormal hyperechoic lens, lens luxation, or keratolenticular adhesion. Type IV: echoes of the DM and the endothelium are continuous, corneal stroma echo is enhanced, and an abnormal strand of peripheral iris extends to the prominent Schwalbe line, accompanied by iris stroma or pupil heteromorphism and a shallow or flat anterior chamber. CONCLUSION: UBM not only could accurately evaluate the anterior segment abnormalities in CCO infants but also would be a step forward for the management of PA- and RA-associated CCO.

[Effects of pericytes on the leakage of rat corneal neovascularization].

OBJECTIVE: To explore the effects of pericytes on the leakage of rat corneal neovascularization (CNV). METHODS: CNV was induced by micropocket assay in rats. Two eyes of the same rat were divided randomly into experimental and control groups. The experimental group received the VEGF + anti-PDGF-B pellet while the control group the VEGF + PBS pellet. Corneal samples were excised at Day 5 postoperation. CNV leakage was measured by Evans blue method. Pericyte coverage index (MPI) was applied to quantify the pericyte coverage through double immunofluorescent stain of frozen sections of corneas with CD31 as endothelial and α-smooth muscle actin (α-SMA) as pericyte marker. Corneal weight was measured. RESULTS: In the control group, MPI was 56.5%, cornea weight (7.36 ± 0.56) mg and CNV permeability rate (0.24 ± 0.07) µg×ml(-1)×mm(-2). In the experimental group, MPI was 11.3%, cornea weight (8.96 ± 1.09) mg and CNV permeability rate (0.68 ± 0.36) µg×ml(-1)×mm(-2). The intergroup difference was statistically significant (P MPI<0.01, P permeability= 0.01, P weight = 0.01). CONCLUSION: Pericytes inhibit the leakage of rat CNV. Such findings may guide the clinical management of hyperpermeability.

Study of the retinal imaging and output in premature baby under a computer-assisted binocular indirect ophthalmoscope.

PURPOSE: To explore a clear retinal imaging and output and enhance the development of retinopathy of prematurity (ROP) screening, which is safe and effective for ROP screening in premature infants. METHODS: A computer-assisted binocular indirect ophthalmoscope imaging and output system was equipped with camera and image processing hardware and connected to computers. The process of fundus examination was videotaped (photograph) and output. Simulated eyes were utilized to debug video head and acquire stable and clear fundus images by binocular indirect ophthalmoscope for premature infants. RESULTS: Fundus imaging output technique was sucessfully established. The common reasons of unclear imaging and corresponding solutions were summarized. This technique can capture and output stable and clear fundus images of premature infants. CONCLUSION: Assisted by hardware and software processing, a compute assisted binocular indirect ophthalmoscope imaging and output system was established, which can be used for screening, research, treatment and follow-up of ROP in premature babies to resolve the difficulty in obtaining clear fundus photograph.

[Impact of lacrimal obstruction type on the efficacy of probing for congenital nasolacrimal duct obstruction].

OBJECTIVE: To explore the impact of lacrimal obstruction type on the efficacy of lacrimal probing in the treatment of congenital nasolacrimal duct obstruction. METHODS: We conducted a retrospective study in which 872 eyes of 741 children with congenital nasolacrimal duct obstruction underwent nasolacrimal duct probing under superficial anesthesia. Two types of obstructions were encountered during probing, i.e. simple and complex. They were divided into early (4 - 12 months) and late (1 - 4 years) groups based upon the age at the time of initial probing. Those refractory to the first probing underwent a second probing 4 weeks later. The main observation criterion was the success rate of probing. RESULTS: The success rate was 90.0% in early group versus 70.4% in late group (χ(2) = 38.527, P < 0.01). No significant difference existed in the cure rate of simple or complex obstruction between two groups (χ(2) simple = 0.054, P = 0.815, χ(2) complex = 1.705, P = 0.192). The proportion of simple obstruction was 94.4% in early group versus 62.2% in late group. Difference was statistically significant (χ(2) = 125.471, P < 0.01). The success rate of a second probing of simple obstruction was 61.9% in early group versus 68.2% in late group (χ(2) = 0.324, P = 0.569). The success rate of a second probing of complex obstruction was 19.2% in early group versus 5.7% in late group (Fisher's exact test, P = 0.125). For either group, the success rate of a second probing of simple obstruction was higher than that of complex obstruction (χ(2) early group = 16.100, P < 0.01; χ(2) late group = 25.186, P < 0.01). CONCLUSION: Unsuccessful probing may result from the selection of complex obstructions. Probing should remain the first-line treatment in children above 1 year of age. The success rate with a second probing was significantly lower in patients of complex obstruction. Other surgical interventions, such as silicone tube intubation or balloon dacryocystoplasty, should be recommended instead of repeated probing for the patients of complex obstruction if an initial probing fails.