Müller cells under hydrostatic pressure modulate retinal cell survival via TRPV1/PLCγ1 complex-mediated calcium influx in experimental glaucoma.

Glaucoma, an irreversible blinding eye disease, is currently unclear whose pathological mechanism is. This study investigated how transient receptor potential cation channel subfamily V member 1 (TRPV1), 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCγ1), and P2X purinoceptor 7 (P2X7) modulate the levels of intracellular calcium ions (Ca2+) and adenosine triphosphate (ATP) in Müller cells and retinal ganglion cells (RGCs) under conditions of elevated intraocular pressure (IOP). Müller cells were maintained at hydrostatic pressure (HP). TRPV1- and PLCG1-silenced Müller cells and P2X7-silenced RGCs were constructed by transfection with short interfering RNA (siRNAs). RGCs were cultured with the conditioned media of Müller cells under HP. A mouse model of chronic ocular hypertension (COH) was established and used to investigate the role of TRPV1 in RGCs in vivo. Müller cells and RGCs were analyzed by ATP release assays, intracellular calcium assays, CCK-8 assays, EdU (5-ethynyl-2'-deoxyuridine) staining, TUNEL staining, flow cytometry, and transmission electron microscopy. In vivo changes in inner retinal function were evaluated by hematoxylin and eosin (H&E) staining and TUNEL staining. Western blot analyses were performed to measure the levels of related proteins. Our data showed that HP increased the levels of ATP and Ca2+ influx in Müller cells, and those increases were accompanied by the upregulation of TRPV1 and p-PLCγ1 expression. Suppression of TRPV1 or PLCG1 expression in Müller cells significantly decreased the ATP levels and intracellular Ca2+ accumulation induced by HP. Knockdown of TRPV1, PLCG1, or P2X7 significantly decreased apoptosis and autophagy in RGCs cultured in the conditioned media of HP-treated Müller cells. Moreover, TRPV1 silencing decreased RGC apoptosis and autophagy in the in vivo model of COH. Collectively, inhibition of TRPV1/PLCγ1 and P2X7 expression may be a useful therapeutic strategy for managing RGC death in glaucoma.

The influence of pterygium on corneal densitometry evaluated using the Oculus Pentacam system.

Purpose: To assess the effect of pterygium on corneal densitometry (CD) values. Methods: One hundred and nine patients (155 eyes) with primary pterygium were divided into a severe pterygium group (79 eyes) and a mild-to-moderate pterygium group (76 eyes) according to pterygium severity. Among them, 63 patients had monocular pterygium; and 25 patients (38 eyes) underwent pterygium excision combined with conjunctival autograft follow-up. A Pentacam anterior segment analyzer was used to obtain the CD values and corneal morphological parameters, including central corneal thickness (CCT), flat-axis keratometry (K1), steep-axis keratometry (K2), corneal astigmatism, irregular astigmatism, and spherical aberration. CD was subdivided into four concentric radial regions based on corneal diameter and three layers according to depth. Results: CD values at 0-12 mm of the anterior 120 µm layer, 0-10 mm of the center layer and full thickness, and 2-6 mm of the posterior 60 µm layer were significantly higher in eyes affected by pterygium than in the contralateral unaffected eyes (all P < 0.05). CD values were significantly higher in the severe pterygium group than in the mild to moderate pterygium group (all P < 0.05). Corneal astigmatism, irregular astigmatism, K1, K2, CCT, and spherical aberration correlated with CD values in eyes with pterygium (all P < 0.05). CD values at 6-10, 0-12 mm in the anterior 120 µm layer and full thickness, 10-12 and 0-12 mm in the center layer were significantly decreased 1 month after pterygium surgery compared with those before surgery (all P < 0.05). Conclusion: Patients with pterygium had increased CD values, particularly in the anterior and central layers. CD values were correlated with pterygium severity grading and corneal parameters. Pterygium surgery partially reduced the CD values.

Age-related changes in Scheimpflug corneal densitometry and their correlations with corneal topographic measurements in a healthy Chinese population.

Background: Objective measurement of corneal densitometry (CD) values can be used to assess corneal transparency and health status, to investigate corneal diseases, and to review anterior segment surgeries. However, literature regarding the association between CD and corneal parameters in healthy adolescent and older individuals is limited. This study investigated age-related changes in Scheimpflug CD values and their correlations with age, sex, and corneal topographic parameters. Methods: This retrospective cross-sectional observational study included 347 eyes from 181 consecutive healthy Chinese participants aged between 5 and 90 years. They were divided into 9 age groups: 5-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-90 years. CD and corneal topographic measurements were measured using the Oculus Pentacam. To evaluate CD, the cornea was divided into 3 layers according to depth (anterior 120 µm, central, and posterior 60 µm), and into 4 annular regions according to diameter (0-2, 2-6, 6-10, and 10-12 mm). Results: CD across different depths and regions was positively correlated with age (all P values <0.001). Of the 3 layers of corneal thickness, CD was highest in the anterior 120 µm and lowest in the posterior 60 µm (all P values <0.05). Among the 4 annular regions spanning the corneal diameter, the lowest CD values were 6-10, 2-6, and 0-2 mm at 5-29, 30-69, and 70-89 years, respectively. The highest CD values were 10-12 mm at 5-79 years, and 6-10 mm at 80-90 years (all P values <0.05). CD values of 10-12 mm in the anterior 120 µm corneal layer were significantly lower in men than in women (Z=-2.353; P=0.019). CD of 0-10 mm in each layer was not significantly different between sexes (all P values >0.05). Corneal topographic measurements, including flat-axis keratometry (K1), steep-axis keratometry (K2), and spherical aberration, were slightly positively correlated with age and CD (all P values <0.05). However, central corneal thickness (CCT) and thinnest corneal thickness (TCT), and age or CD showed no correlation (all P values >0.05). Conclusions: With age, CD, keratometry, and spherical aberration gradually increased, while the corneal thickness did not change significantly.

Polar value analysis of astigmatic change and rotational stability after implantation of V4c toric implantable collamer lens.

BACKGROUND: To evaluate the clinical results and rotational stability of V4c toric implantable collamer lens (TICL, STAAR Surgical Company, Monrovia, CA, USA) in patients with moderate to high myopic astigmatism. Retrospective, interventional case series was performed at Shenzhen Eye Hospital, Shenzhen, Guangdong, China. METHODS: This study enrolled 43 patients (72 eyes) who received TICL implantation to correct myopia and myopic astigmatism. The patients underwent visual and refractive examinations before and 1 month after surgery. Astigmatic changes were estimated using polar value analysis. The difference between the achieved axis and the intended axis at the last follow-up was taken as the rotation of the V4c TICL. RESULTS: At 1 month postoperatively, the mean safety and efficacy indices were 1.17 and 1.13, respectively. A significant reduction of 8.92±2.58 D was observed in the spherical equivalent refraction (SER), which decreased from -9.29±2.41 D preoperatively to -0.37±0.55 D postoperatively. The astigmatic error of treatment in cylinder format was calculated to 0.50±0.41 @ 15.08° relative to the preoperative stronger meridian at 1 month, postoperatively. At 1 month postoperatively, the mean absolute rotation was 8.30±10.00 degrees (median =5.46 degrees; range, 0.00-58.88 degrees). CONCLUSIONS: TICL could achieve good astigmatic outcomes for correcting moderate to high myopic astigmatism. After TICL implantation, corneal astigmatism remained unchanged. To optimize postoperative astigmatic outcomes in TICL, polar value analysis can be used to build a nomogram.

Involvement of the JNK signaling in granular corneal dystrophy by modulating TGF-ß-induced TGFBI expression and corneal fibroblast apoptosis.

Granular corneal dystrophy (GCD) is featured by corneal deposits of transforming growth factor beta-induced gene (TGFBI) mediated by the TGF-ß (transforming growth factor-ß)/Smad signaling. However, the roles of c-Jun amino-terminal kinase (JNK) pathway in GCD pathogenesis remains unexplored, which was investigated in this study. JNK signaling activation and inhibition in primary corneal fibroblasts were obtained by treatments with anisomycin and SP600125, respectively. Protein abundance and phosphorylation were detected by immunoblotting. Cell viability and apoptosis were analyzed by CCK-8 and flow cytometry respectively. TGFBI deposit and autophagy progression were assessed by immunofluorescence. The results found that JNK1 expression and phosphorylation were greatly increased in corneal tissues from GCD2 patients. JNK signaling activation impaired the viability and promoted apoptosis and autophagy processes in primary corneal fibroblasts, along with Smad2/3 phosphorylation, TGFBI accumulation and Bcl-2 suppression. Autophagy related proteins, such as ATG5 (autophagy related 5), ATG12 (autophagy related 12) and LC3B (microtubule-associated protein 1 light chain 3 beta), were also increased in anisomycin or TGF-ß1 treated corneal fibroblasts. However, SP600125 effectively reversed the above effect induced by TGF-ß1 treatment in corneal fibroblasts, including the TGF-ß-induced autophagy progression. The results suggested that JNK signaling was activated in GCD2 corneal tissues, and it mediated the TGF-ß-induced TGFBI protein accumulation and apoptosis of corneal fibroblasts during GCD2 pathogenesis.

Structural Evolution and Compositional Modulation of ZIF-8-Derived Hybrids Comprised of Metallic Ni Nanoparticles and Silica as Interlayer.

Great efforts on metal-organic framework (MOF) derived nanostructures have been devoted to modulating the compositional and structural complexities to enhance performance in various applications. However, a facile method that can simultaneously manipulate the structures of the MOF-derived material and the chemical component remains a considerable challenge. Here we report a facile strategy to use the polyhedral ZIF-8 as a precursor for synthesizing ZIF-8-derived hybrids with different components and morphologies. The synthesis involves the preparation of ZIF-8 MOF templates and sequential covering of the ZIF-8 with a interlayer of silica and then polydopamine-Ni2+ (PDA-Ni2+) and carbonizing at different high temperatures under a nitrogen atmosphere, finally leading to ZIF-8-derived hybrids with different components and structures. In the whole process, the preliminary ZIF-8 precursor play a crucial role in the morphology and structure of the final carbonized products, which can be considered as templates for silica coating and precursors of N-doped carbon layer and Zn species. We also found that the SiO2 interlayer coating is a crucial procedure for the formation of yolk-shell structured ZIF-8@SiO2@PDA-Ni2+ composites. Owing to the uniformly distributed Ni NPs and unique structures of the composites, the as-prepared Ni-based composites show high performance in the catalysis of 4-nitrophenol as well as enrichment of histidine-rich proteins. In addition, this proposed strategy for the controllable design and synthesis of ZIF-8-derived nanocomposites paves a new way in developing superior active materials in energy storage conversion etc.

Association of WDR36 polymorphisms with primary open angle glaucoma: A systematic review and meta-analysis.

BACKGROUND: The association of the WDR36 gene with glaucoma has been controversial in the literature. We therefore conducted a systematic review and meta-analysis to assess the association of all reported common polymorphisms in WDR36 with primary open angle glaucoma (POAG) and its subtypes: high tension glaucoma (HTG) and normal tension glaucoma (NTG). METHODS: Publications in PUBMED and EMBASE databases up to March 9, 2016 were searched for case-control association studies of WDR36 with POAG, HTG, and/or NTG. Reported studies giving adequate genotype and/or allele information were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of individual polymorphisms were estimated using the allelic model. RESULTS: Our literature search yielded 122 records, among which 5 studies were eligible for meta-analysis, involving a total of 1352 POAG patients and 894 controls. Five WDR36 polymorphisms were meta-analyzed, rs11241095, rs10038177, rs17553936, rs13186912, and rs13153937. However, none of them was significantly associated with POAG, HTG, or NTG. The most-investigated polymorphisms, rs11241095 and rs10038177, had a pooled-OR of 1.09 (95% CI: 0.94-1.28, P = .25, I = 0) and 0.99 (95% CI: 0.71-1.39, P = .97, I = 77%), respectively, for POAG. CONCLUSION: The existing data in the literature do not support a significant role of WDR36 in the genetic susceptibility of POAG or its subtypes. Further replication studies in specific populations are warranted.

[Quality evaluation of Astragali Radix through chemical pattern recognition of fingerprint by HPLC-dAD-ELSD].

OBJECTIVE: To develop an HPLC-DAD-ELSD method for detecting the fingerprint of Astragali Radix and evaluate the quality through similarity calculation and chemical pattern recognition. METHOD: Separation was performed at 25 degreeC on an Agilent Zorbax ODS C18 column(4.6 mm x250 mm,5 microm). Gradient elution was performed with the mobile phases of acetonitrile and water containing 0. 2% formic acid. The flow rate was 0. 8 mL min-1 , and sample size was 10 microL. The UV detection wavelength was set at 280 nm. The drift tube temperature for ELSD was set at 110 degreeC , and the nebulizing gas flow rate was 3.0 L min-1. The similarity calculation and chemical pattern recognition were used for fingerprint analysis. RESULT: The HPLC-DAD-ELSD method for chromatographic fingerprint of Astragali Radix showed better results of stability, precision and repeatability. The reference chromatographic fingerprint of Astragali Radix was established on the eighteen Astragali Radix samples from different sources. The results of similarity calculation were higher than 0. 83, which was in accordance with the result of chemical pattern recognition analysis. CONCLUSION: Fingerprint and chemical pattern recognition analysis could effectively distinguish Astragali Radix from different source, which could be applied to the quality control of Astragali Radix.