TRB3 Promotes Cataract Progression through Endoplasmic Reticulum Stress-mediated Mitochondrial Dysfunction and Cell Apoptosis.

Cataracts are characterized as a disease affecting lens opacity. Endoplasmic reticulum (ER) stress can cause lens epithelial cell (LEC) dysfunction, affecting normal lens transparency and function, but the role of Tribbles 3 (TRB3), an inducible gene of ER stress, in cataracts is poorly understood. This study explored how TRB3 promotes cataract progression through ER stress. We administered a subcutaneous injection of sodium selenite at a dosage of 3.46 mg/kg to rats to create an animal model of cataracts. Additionally, we exposed rat LEC cells to 0.01 µM tunicamycin (TM) for 24 h to establish a cell model of ER stress. The detection of related genes and proteins was performed via RT‒qPCR and Western blot techniques. Flow cytometry, along with JC-1, TUNEL, and HE staining, was employed to assess damage to cells and lens tissues. This study revealed that TRB3 was abnormally highly expressed in both a cataract rat model and an ER stress cell model. Knocking down TRB3 has a similar effect as treatment with an ER stress inhibitor, effectively reversing the ER stress and apoptosis induced by TM. This effect includes increasing the mitochondrial membrane potential in LEC cells, lowering reactive oxygen species (ROS) levels, increasing ATP production, suppressing the expression of the apoptosis-related proteins Bax and C-caspase-3, increasing Bcl-2 expression, and decreasing apoptosis. Furthermore, TRB3 knockdown improved the pathological conditions of rat lenses and inhibited mitochondrial dysfunction and cell apoptosis to relieve the development of cataracts in rats. Mechanistically, CHOP promotes the expression of TRB3 by binding to the TRB3 promoter, thereby activating ER stress, leading to mitochondrial dysfunction and cell apoptosis in LEC cells and accelerating the development of cataracts. According to our findings, targeting TRB3 expression inhibition could emerge as a novel approach for cataract therapy.

Role of C/EBP Homologous Protein (CHOP) and Nupr1 Interaction in Endoplasmic Reticulum Stress-Induced Apoptosis of Lens Epithelial Cells.

Our study mainly analyzed the mechanism of C/EBP homologous protein (CHOP) and its interacting protein Nupr1 on endoplasmic reticulum stress (ERS) induced lens epithelial cells (LEC) apoptosis. Cell proliferation was detected by CCK-8. Apoptosis was detected by flow cytometry and TUNEL. Nupr1 expression was detected by RT-qPCR. The expressions of CHOP, Nupr1, apoptosis-related protein, and ERS-related protein were detected by Western blot. DCFH-DA probe was used to detect cell ROS. The SOD, GSH-PX, and MDA contents were detected by the kit. Co-IP was used to detect the interaction between CHOP and Nupr1. The morphology of the lens was detected by HE staining. The result shows that Tunicamycin (TU) can induce endoplasmic reticulum stress and apoptosis in LEC in a concentration-dependent manner. TU induction leads to the occurrence of CHOP nuclear translocation. Overexpression of CHOP can further enhance the inhibitory effect of TU on LEC proliferation and the promotion of apoptosis, while knockdown of CHOP has the opposite effect. CHOP and Nupr1 are interacting proteins, and knockdown of Nupr1 or addition of Nupr1 inhibitor ZZW-115 can reverse the effects of TU and overexpression of CHOP, respectively. It has been observed in animal experiments that treatment with oe-CHOP can further aggravate the pathological lesions of the rat lens, while ZZW-115 can reverse the effect of oe-CHOP to a certain extent and improve the lesions of the rat lens. Overall, CHOP interacts with Nupr1 to regulate apoptosis caused by ERS and mediate cataract progression in rats, and this study provides a new potential therapeutic target for the treatment of cataract.

Preliminary Study on the Correlation Between Episcleral Venous Pressure and Intraocular Pressure in TAO Patients and Its Clinical Value.

Objective: To study the correlation between episcleral vein pressure (EVP) with intraocular pressure (IOP), exophthalmos, and optic nerve injury in thyroid-associated ophthalmopathy (TAO) patients and to explore the possibility of higher EVP as an intervention indicator in TAO patients. Methods: This study was a case-control study, including the TAO group and normal control group. TAO group: 15 patients (30 eyes) were diagnosed with TAO complicated with exophthalmos. Normal control group: 14 cases, 28 eyes. EVP, IOP, exophthalmos, retinal nerve fiber layer thickness, and visual field were measured, respectively in the two groups. Non-parametric test was used to compare the difference between EVP and IOP between the two groups, test the correlation between EVP and IOP or exophthalmos, and analyze the clinical characteristics of optic nerve injury in patients with elevated IOP in the TAO group. Results: The EVP in the TAO group (15.30±3.48 mmHg) was significantly higher than the normal control group (8.82±1.44 mmHg) (P < .001). The IOP in the TAO group (18.55±8.13 mmHg) was significantly higher than in the normal control group (12.98±2.10 mmHg) (P < .001) (3) There was a positive linear correlation between EVP (X) and IOP (Y) in TAO group: Y = 0.9684x + 3.737 (rs>0, P < .05); There was a positive linear correlation between EVP (Y) and exophthalmos (X) in TAO group: Y = 0.9218x - 2.691 (rs>0, P < .05); Some TAO patients with elevated EVP had the related manifestations of optic nerve function impairment: thinning of retinal nerve fiber layer and loss of visual field. However, there was no clear correlation between EVP and the thickness of the optic nerve fiber layer (P = .4354). Conclusion: The increase of EVP is an important factor leading to elevated IOP in TAO patients, which may be used as an indicator for intervention treatment in TAO patients. EVP can be used to indirectly evaluate orbital pressure. TAO patients can develop secondary glaucoma with irreversible optic nerve damage due to the continuous Elevation of EVP.

Circ-CARD6 inhibits oxidative stress-induced apoptosis and autophagy in ARPE-19 cells via the miR-29b-3p/PRDX6/PI3K/Akt axis.

BACKGROUND: Oxidative stress-induced damage and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD) and hereditary retinopathy diseases (HRDs). This study aimed to elucidate the roles and mechanisms of circ-CARD6 and miR-29b-3p in oxidative stress-induced RPE and provide new ideas for the diagnosis and treatment of retinopathy disease (RD). METHODS: A model of oxidative stress-induced RPE (ARPE-19) was established, and the level of malondialdehyde (MDA) and concentration of reactive oxygen species (ROS) were detected by a DCFH-DA fluorescent probe and MDA kit. The cell viability was measured by a CCK-8 assay. The expression of PRDX6/PI3K/Akt axis genes and proteins related to apoptosis and autophagy were determined by RT‒qPCR and Western blot analyses. The dual-luciferase reporter system confirmed the targeting relationship between miR-29b-3p and circ-CARD6 and between miR-29b-3p and PRDX6. RESULTS: In H2O2-treated ARPE-19 cells, the expression of circ-CARD6 and PRDX6 was decreased, while the expression of miR-29b-3p was increased. The overexpression of circ-CARD6 inhibits oxidative stress-induced increases in ROS, apoptosis and autophagy in ARPE-19 cells. circ-CARD6 targets miR-29b-3p, miR-29b-3p targets PRDX6, and circ-CARD6 regulates PRDX6 via miR-29b-3p. Further studies showed that circ-CARD6 acts as a competitive endogenous RNA of miR-29b-3p to affect the expression of PRDX6, thereby inhibiting autophagy and apoptosis in ARPE-19 cells. CONCLUSION: circ-CARD6 can inhibit oxidative stress and apoptosis by regulating the miR-29b-3p/PRDX6/PI3K/Akt axis.

A novel missense mutation in the CRYBA2 caused autosomal dominant presenile cataract in a Chinese family.

Presenile cataract is a relatively rare type of cataract, but its genetic mechanisms are currently not well understood. The precise identification of these causative genes is crucial for effective genetic counseling for patients and their families. The aim of our study was to identify the causative gene associated with presenile cataract in a Chinese family. In February 2020, a four-generation pedigree of presenile cataract patients was recruited at the 2nd Affiliated Hospital of Kunming Medical University. One patient and her healthy husband from the family underwent whole exome sequencing. The variant was validated through sanger sequencing, and co-segregation analysis was conducted in all family members to assess its pathogenicity. Molecular dynamics simulation (MDS) was used to analyze the conformation of both the wild type and pathogenic mutant loci p.Y153H of CRYBA2. We identified presenile cataract in the pedigree, which follows an autosomal-dominant pattern of inheritance. The family includes five clinically affected patients who all developed presenile cataract between the ages from 24 to 30. We confirmed the pathogenicity of a heterozygous missense variant (NM_057093:c.457T >C) in CRYBA2 within this family. The affected amino acid demonstrates high conservation across species. Subsequent sanger sequencing confirmed co-segregation of the disease in all family members. MDS analysis revealed that the p.Y153H mutant disrupted hydrogen bond formation between Y153 and R193 within the two ß-strands of the fourth Greek key domain, leading to destabilization of the ßA2-crystallin. In conclusion, a novel causative mutation (NM_057093:c.457T>C) in CRYBA2 might contribute to autosomal dominant presenile cataract.

Dynamic nomogram prediction model for diabetic retinopathy in patients with type 2 diabetes mellitus.

BACKGROUND: To develop a dynamic prediction model for diabetic retinopathy (DR) using systemic risk factors. METHODS: This retrospective study included type 2 diabetes mellitus (T2DM) patients discharged from the Second Affiliated Hospital of Kunming Medical University between May 2020 and February 2022. The early patients (80%) were used for the training set and the late ones (20%) for the validation set. RESULTS: Finally, 1257 patients (1049 [80%] in the training set and 208 [20%] in the validation set) were included; 360 (28.6%) of them had DR. The areas under the curves (AUCs) for the multivariate regression (MR), least absolute shrinkage and selection operator regression (LASSO), and backward elimination stepwise regression (BESR) models were 0.719, 0.727, and 0.728, respectively. The Delong test showed that the BESR model had a better predictive value than the MR (p = 0.04899) and LASSO (P = 0.04999) models. The DR nomogram risk model was established according to the BESR model, and it included disease duration, age at onset, treatment method, total cholesterol, urinary albumin to creatinine ratio (UACR), and urine sugar. The AUC, kappa coefficient, sensitivity, specificity, and compliance of the nomogram risk model in the validation set were 0.79, 0.48, 71.2%, 78.9%, and 76.4%, respectively. CONCLUSIONS: A relatively reliable DR nomogram risk model was established based on the BESR model.

Integrin ligands block mechanical signal transduction in baroreceptors.

Baroreceptors are nerve endings located in the adventitia of the carotid sinus and aortic arch. They act as a mechanoelectrical transducer that can sense the tension stimulation exerted on the blood vessel wall by the rise in blood pressure and transduce the mechanical force into discharge of the nerve endings. However, the molecular identity of mechanical signal transduction from the vessel wall to the baroreceptor is not clear. We discovered that exogenous integrin ligands, such as RGD, IKVAV, YIGSR, PHSRN, and KNEED, could restrain pressure-dependent discharge of the aortic nerve in a dose-dependent and reversible manner. Perfusion of RGD at the baroreceptor site in vivo can block the baroreceptor reflex. An immunohistochemistry study showed the binding of exogenous RGD to the nerve endings under the adventitia of the rat aortic arch, which may competitively block the binding of integrins to ligand motifs in extracellular matrix. These findings suggest that connection of integrins with extracellular matrix plays an important role in the mechanical coupling process between vessel walls and arterial baroreceptors.

miR-181d-5p Protects against Retinal Ganglion Cell Death after Blunt Ocular Injury by Regulating NFIA-Medicated Astrocyte Development.

Background: Traumatic optic neuropathy (TON) refers to damage to the optic nerve resulting from direct and indirect trauma to the head and face. One of the important pathological processes in TON is the death of retinal ganglion cells (RGCs), but the cause of RGCs death remains unclear. We aimed to explore the mechanisms of RGCs death in an experimental TON model. Methods: Optic nerve crush injury was induced in ten New Zealand white rabbits. On the 1st, 3rd, 7th, 14th, and 28th days after the operation, the retinal tissues of the rabbits were observed pathologically by hematoxylin-eosin staining. The expression of POU-homeodomain transcription factor Brn3a and glial fibrillary acidic protein (GFAP) was measured by immunofluorescence to evaluate the number of RGCs and astrocytes, respectively. miRNA expression and protein levels were assessed by RT-qPCR and western blot methods, respectively. Finally, the malondialdehyde content, superoxide dismutase activity, and proinflammatory factor levels were measured by ELISA. Western blot and dual-luciferase reporter assays were used to elucidate the relationship between miR-181d-5p and nuclear factor I-A (NFIA). Results: Blunt ocular trauma increased oxidative stress and apoptosis and reduced ganglion cell layer (GCL) density. The expression of miR-181d-5p was decreased in retinal tissues, and its overexpression relieved RGCs death, astrocyte development, oxidative stress, and inflammation of the retina, which were reversed by NFIA overexpression. Conclusion: miR-181d-5p can protect against the deterioration of TON by inhibiting RGCs death, astrocyte development, oxidative stress, and inflammation by targeting NFIA. This study provides new insight into early medical intervention in patients with TON.

5-HT2B-mediated serotonin activation in enterocytes suppresses colitis-associated cancer initiation and promotes cancer progression.

Rationale: Serotonin (5-hydroxytryptamine, 5-HT) is generally considered to be involved in colitis-associated cancer (CAC), but previous research has yielded inconsistent results regarding the effect of 5-HT on CAC. 5-HT2B is one of the receptors of 5-HT, and the receptor is expressed in intestinal epithelial cells (IECs). However, the functions of 5-HT2B in CAC remain unclear. Our work demonstrates the variable functions of 5-HT/5-HT2B signaling in the initiation and progression of CAC in mice. Methods: We constructed two types of mutant mice homozygous knockout of Htr2b, the gene encoding 5-HT2B, in IECs (Htr2bΔIEC and Htr2bΔIEC-ER) to study the role of 5-HT2B in AOM/DSS-induced CAC model. Inflammation was measured using the body weight, colon length, and colitis severity score, and by histologic analysis of colon tissues. Tumor severity was assessed by tumor quantity, load, and histologic analysis of colon tumor tissues. Results: In Htr2bΔIEC mice, AOM/DSS induced an enhancement of colitis and tumor severity. This process was due to the inhibition of TGF-ß/SMAD signaling pathway and activation of IL-6/STAT3 signaling pathway. IL-6 antibody treatment reversed the stimulating effect of Htr2b deletion on tumorigenesis. However, tumor severity decreased in Htr2bΔIEC-ER mice injected with tamoxifen on day 48 of AOM/DSS treatment. Knockout Akt1 eliminated the function of 5-HT in promoting tumor cells. Conclusion: Our work elucidates 5-HT/5-HT2B/TGF-ß signaling as a critical tumor suppressing axis during CAC initiation but as a promoter of cancer progression in the late-stage of CAC. Our findings provide a new understanding of the role of 5-HT in the initiation and progression of CAC, offering a new perspective on the long-standing debate on whether the 5-HT signal promotes or inhibits tumors.

Characteristics of the Peritrophic Matrix of the Silkworm, Bombyx mori and Factors Influencing Its Formation.

The peritrophic matrix (PM) secreted by the midgut cells of insects is formed by the binding of PM proteins to chitin fibrils. The PM envelops the food bolus, serving as a barrier between the content of the midgut lumen and its epithelium, and plays a protective role for epithelial cells against mechanical damage, pathogens, toxins, and other harmful substances. However, few studies have investigated the characteristics and synthesis factors of the PM in the silkworm, Bombyx mori. Here, we examined the characteristics of the PM in the silkworms. The PM thickness of the silkworms increased gradually during growth, while there was no significant difference in thickness along the entire PM region. Permeability of the PM decreased gradually from the anterior to posterior PM. We also found that PM synthesis was affected by food ingestion and the gut microbiota. Our results are beneficial for future studies regarding the function of the PM in silkworms.

Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons.

Macroautophagy/autophagy is vital for neuronal homeostasis and functions. Accumulating evidence suggest that autophagy is impaired during cerebral ischemia, contributing to neuronal dysfunction and neurodegeneration. However, the outcomes after transient modification in autophagy machinery are not fully understood. This study investigated the effects of ischemic stress on autophagy and synaptic structures using a rat model of oxygen-glucose deprivation (OGD) in hippocampal neurons and a mouse model of middle cerebral artery occlusion (MCAO). Upon acute ischemia, an initial autophagy modification occurred in an upregulation manner. Following, the number of lysosomes increased, as well as lysosomal volume, indicating dysfunctional lysosomal storage. These changes were prevented by inhibiting autophagy via 3-methyladenine (3-MA) treatment or ATG7 (autophagy related 7) knockdown, or were mimicked by rapamycin (RAPA), a known activator of autophagy. This suggests that dysfunctional lysosomal storage is associated with the early burst of autophagy. Dysfunctional lysosomal storage contributed to autophagy dysfunction because the basal level of MTOR-dependent lysosomal biogenesis in the reperfusion was not sufficient to clear undegraded cargoes after transient autophagy upregulation. Further investigation revealed that impairment of synaptic ultra-structures, accompanied by dysfunctional lysosomal storage, may result from a failure in dynamic turnover of synaptic proteins. This indicates a vital role of autophagy-lysosomal machinery in the maintenance of synaptic structures. This study supports previous evidence that dysfunctional lysosomal storage may occur following the upregulation of autophagy in neurons. Appropriate autophagosome-lysosomal functioning is vital for maintenance of neuronal synaptic function and impacts more than the few known synaptic proteins.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AD: Alzheimer disease; ALR: autophagic lysosome reformation; ATG7: autophagy related 7; CTSB: cathepsin B; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; DEGs: differentially expressed genes; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; GO: Gene Ontology; HBSS: Hanks' balanced salt solution; HPCA: hippocalcin; i.c.v: intracerebroventricular; KEGG: kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; LSDs: lysosomal storage disorders; MAP2: microtubule-associated protein 2; MCAO: middle cerebral artery occlusion; mCTSB: mature CTSB; mCTSD: mature CTSD; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; OGD/R: oxygen-glucose deprivation/reoxygenation; PBS: phosphate-buffered saline; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; proCTSD: pro-cathepsin D; RAPA: rapamycin; RNA-seq: RNA sequencing; RPS6KB/p70S6K: ribosomal protein S6 kinase; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SIM: Structured Illumination Microscopy; SNAP25: synaptosomal-associated protein 25; SQSTM1/p62: sequestosome 1; SYN1: synapsin I; SYT1: synaptotagmin I; TBST: tris-buffered saline Tween-20; TEM: transmission electron microscopy; TFEB: transcription factor EB; tMCAO: transient middle cerebral artery occlusion; TTC: 2,3,5-triphenyltetrazolium chloride; TUBB3: tubulin, beta 3 class III.

Identification of Peritrophins and Antiviral Effect of Bm01504 against BmNPV in the Silkworm, Bombyx mori.

The insect midgut secretes a semi-permeable, acellular peritrophic membrane (PM) that maintains intestinal structure, promotes digestion, and protects the midgut from food particles and pathogenic microorganisms. Peritrophin is an important PM protein (PMP) in the PM. Here, we identified 11 peritrophins with 1-16 chitin binding domains (CBDs) comprising 50-56 amino acid residues. Multiple CBDs in the same peritrophin clustered together, rather than by species. The CBD contained six highly conserved cysteine residues, with the key feature of amino acids between them being CX11-15CX5CX9-14CX11-12CX6-7C. Peritrophins with 2 and 4 CBDs (Bm09641 and Bm01504, respectively), and with 1, 8, and 16 CBDs (Bm11851, Bm00185, and Bm01491, respectively) were mainly expressed in the anterior midgut, and throughout the midgut, respectively. Survival rates of transgenic silkworms with Bm01504 overexpression (Bm01504-OE) and knockout (Bm01504-KO) infected with B. morinucleopolyhedrovirus (BmNPV) were significantly higher and lower, whereas expression of the key viral gene, p10, were lower and higher, respectively, compared with wild type (WT). Therefore, Bm01504-OE and Bm01504-KO transgenic silkworms were more and less resistant, respectively, to BmNPV. Bm01504 plays important roles in resisting BmNPV invasion. We provide a new perspective for studying PM function, and reveal how the silkworm midgut resists invasive exogenous pathogenic microorganisms.

Differential metabolic markers associated with primary open-angle glaucoma and cataract in human aqueous humor.

BACKGROUND: We aimed to identify metabolic biomarkers and investigate the metabolic alterations in relation to primary open-angle glaucoma (POAG) and cataract in human aqueous humor. METHODS: Sixteen POAG patients undergoing surgical treatments and 24 patients undergoing cataract surgeries were included in this case-control study. We performed the metabolomic analysis of aqueous humor samples using a non-targeted gas chromatography coupled to time-of-flight mass spectrometer. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacities of each metabolite marker. Databases including the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were utilized to search for the potential pathways of metabolites. RESULTS: Aqueous humor metabolomic profiles could well distinguish POAG from controls. Fourteen metabolic biomarkers were identified as potential aqueous humor biomarkers for POAG, yielding AUC values from 0.62 to 0.86. In pathway analysis, Biotin metabolism was highly impacted, implying that these metabolic markers play important roles in the regulation of this pathway. CONCLUSIONS: This study identified valuable metabolic biomarkers and pathways that may facilitate an improved understanding of the POAG pathogenesis. The finding holds translational value in the development of new therapeutic measures for POAG.

Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8.

Methyltransferase-like protein 3 (METTL3) regulates multiple cell functions and diseases by modulating N6-methyladenosine (m6A) modifications. However, it is still unclear whether METTL3 involves in the pathogenesis of diabetic retinopathy (DR). In the present study, we found that high-glucose inhibited RPE cell proliferation, promoted cell apoptosis and pyroptosis in a time-dependent manner. In addition, both METTL3 mRNA and miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. As expected, upregulation of METTL3 and miR-25-3p alleviated the cytotoxic effects of high-glucose on RPE cells, and knock-down of METTL3 and miR-25-3p had opposite effects. Additionally, METTL3 overexpression increased miR-25-3p levels in RPE cells in a microprocessor protein DGCR8-dependent manner, and miR-25-3p ablation abrogated the effects of overexpressed METTL3 on cell functions in high-glucose treated RPE cells. Furthermore, PTEN could be negatively regulated by miR-25-3p, and overexpression of METTL3 increased phosphorylated Akt (p-Akt) levels by targeting miR-25-3p/PTEN axis. Consistently, upregulation of PTEN abrogated the protective effects of METTL3 overexpression on RPE cells treated with high-glucose. Collectively, METTL3 rescued cell viability in high-glucose treated RPE cells by targeting miR-25-3p/PTEN/Akt signaling cascade.

PRDX6 regulates the H2O2 and blue light-induced APRE-19 cell apoptosis via down-regulating and interacting with RARA.

Hereditary retinal disease (HRD) is the primary retinal degeneration that leads to severe visual impairments and refractory blindness, and the therapy of HRD was most important in ophthalmology. The apoptosis of retinal cells plays important roles in HRD progression. Therefore, in this study, we explore the mechanism of H2O2 and blue light-induced apoptosis of ARPE-19 cells. Co-immunoprecipitation (Co-IP) is employed to test the interactions between proteins, and western blotting is used to detect the protein levels. Apoptosis is analyzed by Flow cytometry. Our results found that PRDX6 could interact with RARA in ARPE-19 cells, and H2O2 and blue light could significantly reduce the RARA protein expression, and also could inhibit the interaction between PRDX6 and RARA. Using a rescue experiment, we further elucidated that H2O2 and blue light reduced the RARA expression via down-regulating PRDX6. And H2O2 and blue light induced the ARPE-19 cell apoptosis via decreasing the expression of PRDX6. Our results suggested that the interaction between PRDX6 and RARA played important roles in the apoptosis of ARPE-19 cells.

A novel nonsense mutation in ADAMTS17 caused autosomal recessive inheritance Weill-Marchesani syndrome from a Chinese family.

Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, glaucoma and occasionally heart defects. Given these complex clinical manifestations and genetic heterogeneity, WMS patients presented misdiagnosed as high myopia or angle closure glaucoma. Here, we report ADAMTS17 mutations, a member of the extracellular matrix protease family, from a Chinese family. Patients have features that fall within the WMS spectrum. The exome (protein-coding regions of the genome) makes up ~1 % of the genome, it contains about 85% of known disease-related variants. Whole exome sequencing (WES) has been performed to identify the disease-associated genes, including one patient, his healthy sister, and his asymptomatic wife. Genome-wide homozygosity map was used to identify the disease caused locus. SNVs and INDELs were further predicted with MutationTaster, LRT, SIFT and SiPhy and compared to dbSNP150 and 1000 Genomes project. Filtered mutation was confirmed with Sanger sequencing in whole family members. The Genome-wide homozygosity map based on WES identified a total of 20 locus which were possible pathogenic. Further, a novel nonsense mutation c.1051A >T result in p.(lys351Ter) in ADAMTS17 had been identified in a candidate loci. The Sanger sequencing data has verified two consanguineous WMS patients in the family pedigree and revealed autosomal recessive (AR) inheritance pattern. The nonsense mutation in ADAMTS17 was analyzed in silico to explore its effects on protein function. We predicted the mutation produced non-function protein sequence. A novel nonsense mutation c.1051 A > T in ADAMTS17 had been identified caused autosomal recessive WMS in the Chinese family.

High-glucose induces retinal pigment epithelium mitochondrial pathways of apoptosis and inhibits mitophagy by regulating ROS/PINK1/Parkin signal pathway.

Diabetic retinopathy (DR) seriously endangers human beings' health, uncovering the underlying mechanism might help to cure DR. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose (50mM) promotes reactive oxygen species (ROS) generation and cell apoptosis, inhibits cell mitophagy as well as proliferative abilities, while low-glucose (15mM) induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose (50mM) on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose (50mM) induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose (50mM) inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose (50mM) or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucose's inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating ROS mediated inactivation of ROS/PINK1/Parkin signal pathway.

[Impacts of electromagnetic radiation from cellphones and Wi-Fi on spermatogenesis].

With the development of Wi-Fi technology and widespread exposure to electromagnetic radiation (EMR), people are increasingly concerned about the health hazards caused by radiofrequency electromagnetic fields as from cellphones and Wi-Fi, particularly about the current decline in sperm concentration and increase in male infertility. Long-term exposure to EMR not only damages male reproductive organs, but also affects the number, morphology, motility and oocyte-binding ability of sperm, and indirectly increases the risk of infertility. However, EMR is not unavoidable. Low-intensity short-term or intermittent exposure to EMR has little adverse effect on reproductive organs and sperm. And many antioxidant and anti-free radical agents, such as vitamin E and melatonin, can protect some special populations from EMR. This review presents an overview of the impacts of EMR from cellphones and Wi-Fi on sperm, some countermeasures, and prospects of EMR protection.

Mutation Analysis of Families with Autosomal Dominant Congenital Cataract: A Recurrent Mutation in the CRYBA1/A3 Gene Causing Congenital Nuclear Cataract.

PURPOSE: To identify the CRYBA1/A3 mutation spectrum and analyze the genotype-phenotype correlations in Chinese families with congenital cataract. METHODS: Family history and clinical data of 47 unrelated families with autosomal dominant congenital cataract (ADCC) were recorded. CRYBA1/A3 gene sequencing was applied to identify the causative mutation. Haplotypes were constructed using closely linked microsatellite markers and intragenic single-nucleotide polymorphisms (SNPs) to compare the affected haplotype in three families. RESULTS: Nuclear cataract was the most common type of ADCC in Chinese families, accounting for 42.6% (20/47). A recurrent CRYBA1/A3 deletion mutation (ΔG91) was identified in three families (6.4%) with nonprogressive nuclear congenital cataract. Different haplotypes segregated with the mutation in each family. CONCLUSIONS: A recurrent ΔG91CRYBA1/A3 mutation occurs independently in 6.4% of the Chinese families with autosomal dominant nuclear cataracts and most likely represents a mutational hot spot, which underscores the relations between nonprogressive nuclear cataract and CRYBA1/A3.

A Nomogram to Improve Predictability of Small-Incision Lenticule Extraction Surgery.

BACKGROUND This study aimed to determine and validate that use of a nomogram could enhance the predictability of small-incision lenticule extraction (SMILE) surgery. MATERIAL AND METHODS 195 eyes from 98 patients were enrolled in group 1, and 46 eyes from 26 patients in group 2. Uncorrected and corrected distance visual acuity (UDVA and CDVA), manifest refraction spherical equivalent (SE) preoperatively and 1 day, 1 week, 1 month, and 3 months postoperatively were measured. A nomogram based on the error in SE correction was generated by using multifactor regression method in group 1. After applying this nomogram to redesign the refraction target, the predictability, safety, and efficacy of the SMILE procedure were determined. RESULTS A linear regression formula (SE error=0.259+0.113×SEpreoperative) was derived as a nomogram to adjust the SE target. In group 2, the predictability of error was 86.21% within 0.50 D and 97.83% within 1.00 D, compared with 70.25% and 95.90%, respectively, in group 1. The use of the nomogram significantly reduced the variance in postoperative SE. The efficacy and safety of SMILE did not differ significantly in the 2 groups 3 months postoperatively. CONCLUSIONS The nomogram can optimize the target refractive prediction of the SMILE procedure without compromising safety and efficiency.