The effect of intense pulsed light combined with topical 0.05% cyclosporin an eyedrops in the treatment of Sjögren's syndrome related dry eye.

OBJECTIVES: This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren's Syndrome-related dry eyes (SS-DE). RESEARCH DESIGN AND METHODS: In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality. RESULTS: Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all p < 0.05). Group C showed a greater increase in OSDI, NBUT, MG expressibility, and meibum quality (all p < 0.05). Moreover, SIT and lid margin abnormalities significantly improved in Group C (both p < 0.05), but not in Group S. CONCLUSION: Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE. CLINICAL TRIAL: Registered on 20 July 2021, with the registration number ChiCTR2100049059.

Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35-762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

Novel treatment of chalazion using light-guided-tip intense pulsed light.

We assessed the effectiveness of light-guided-tip intense pulsed light (IPL) with meibomian gland expression (MGX) in chalazion treatment. Ninety-five eyes with chalazion received a light-guided-tip IPL-MGX treatment (IPL-MGX group), and another 95 eyes with chalazion received incision with curettage treatment (Control group). Prior to IPL or incision, as well as 1 month after the final treatment, data were gathered pertaining to the lesion location and size, hyperemia, lesions regression or recurrence, and a comprehensive ophthalmic examination. The total size of the chalazia in the IPL-MGX group was significantly reduced after the final treatment, with an average resolution rate of 70.5%, which is comparable to excision surgery. A significant decrease in chalazion recurrence rate was apparent after treatment in the IPL-MGX group compared with control. Moreover, the IPL-MGX demonstrated significant advancements throughout noninvasive tear film breakup time (NIBUT) as well as meibum grade in comparison to baseline and those in the the Control group. The use of IPL-MGX was found to be an efficient therapy for reducing the size and recurring frequency of chalazia, as well as for improving the meibomian gland function. It may be considered as a first-line treatment for cases of primary or recurrent chalazia with inflammation.

Postponement of the opacification of lentoid bodies derived from human induced pluripotent stem cells after lanosterol treatment-the first use of the lens aging model in vitro in cataract drug screening.

Purpose: Our previous study observed that human induced pluripotent stem cell (HiPSC)-derived lentoid bodies (LBs) became cloudy with extended culture time, partially mimicking the progress of human age-related cataracts (ARCs) in a dish. In the present study, lanosterol, a potential anticataract drug, was used to further verify the value of this model in drug screening for cataract treatment. Methods: Mature LBs on day 25, which were differentiated from HiPSCs using the "fried egg" method, were continually cultured and treated with either dimethyl sulfoxide (control) or lanosterol. The LBs' shape and opacity alterations were examined using light microscopy and mean gray value evaluation. The soluble and insoluble proteins were examined through SDS-PAGE gel electrophoresis combined with Coomassie blue staining. The protein aggregations were examined with immunofluorescence. Results: The mature LBs became cloudy with an extended culture time, and the opacification of the LBs was partially prevented by lanosterol treatment. There was less increase in insoluble proteins in the lanosterol-treated LBs than in the control group. There were also fewer cells containing aggregated protein (αA-crystallin and αB-crystallin) puncta in the lanosterol-treated LBs than in the control LBs. Conclusion: It was found that the opacification of LBs could be delayed by lanosterol treatment, which could be achieved by reducing protein aggregation, suggesting a promising HiPSC-derived drug-screening model for Age-related cataract.

Exosomes-loaded thermosensitive hydrogels for corneal epithelium and stroma regeneration.

Corneal damage forms scar tissue and manifests as permanent corneal opacity, which is the main cause of visual impairment caused by corneal diseases. To treat these diseases, herein, we developed a novel approach based on the exosome derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) combined with a thermosensitive hydrogel, which reduces scar formation and accelerates the healing process. We found that a thermosensitive chitosan-based hydrogels (CHI hydrogel) sustained-release iPSC-MSC exosomes can effectively promote the repair of damaged corneal epithelium and stromal layer, downregulating mRNA expression coding for the three most enriched collagens (collagen type I alpha 1, collagen type V alpha 1 and collagen type V alpha 2) in corneal stroma and reducing scar formation in vivo. Furthermore, iPSC-MSCs secrete exosomes that contain miR-432-5p, which suppresses translocation-associated membrane protein 2 (TRAM2), a vital modulator of the collagen biosynthesis in the corneal stromal stem cells to avert the deposition of extracellular matrix (ECM). Our findings indicate that iPSC-MSCs secrete miRNA-containing exosomes to promote corneal epithelium and stroma regeneration, and that miR-432-5p can prevent ECM deposition via a mechanism most probably linked to direct repression of its target gene TRAM2. Overall, our exosomes-based thermosensitive CHI hydrogel, is a promising technology for clinical therapy of various corneal diseases.

Establishment of New Genetic Markers and Methods for Sex Determination of Mouse and Human Cells using Polymerase Chain Reactions and Crude DNA Samples.

Background: The currently available methods for sexing human or mouse cells have weaknesses. Therefore, it is necessary to establish new methods. Methods: We used bioinformatics approach to identify genes that have alleles on both the X and Y chromosomes of mouse and human genomes and have a region showing a significant difference between the X and Y alleles. We then used polymerase chain reactions (PCR) followed by visualization of the PCR amplicons in agarose gels to establish these genomic regions as genetic sex markers. Results: Our bioinformatics analyses identified eight mouse sex markers and 56 human sex markers that are new, i.e. are previously unreported. Six of the eight mouse markers and 14 of the 56 human markers were verified using PCR and ensuing visualization of the PCR amplicons in agarose gels. Most of the tested and untested sex markers possess significant differences in the molecular weight between the X- and Y-derived PCR amplicons and are thus much better than most, if not all, previously-reported genetic sex markers. We also established several simple and essentially cost-free methods for extraction of crude genomic DNA from cultured cells, blood samples, and tissues that could be used as template for PCR amplification. Conclusion: We have established new sex genetic markers and methods for extracting genomic DNA and for sexing human and mouse cells. Our work may also lend some methodological strategies to the identification of new genetic sex markers for other organismal species.

Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells.

Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients' cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients' cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment.

Effect of SMILE-derived decellularized lenticules as an adhesion barrier in a rabbit model of glaucoma filtration surgery.

BACKGROUND: To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticules on intraocular pressure (IOP) and conjunctival scarring in a rabbit model of glaucoma filtration surgery. METHODS: Trabeculectomy was performed on both eyes of New Zealand rabbits. A decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (the decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (the control group). The filtering bleb features and IOP were evaluated 0, 3, 7, 14, 21, and 28 days after surgery, and histopathologic examination was performed 28 days after surgery. RESULTS: Decellularized lenticules significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. The histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group. CONCLUSIONS: Decellularized lenticules can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and they may represent a novel antifibrotic agent for trabeculectomy.

[Relationship between occupational noise exposure and hypertension in male steel workers].

OBJECTIVE: To analyze the effect of occupational noise exposure on hypertension in male steel workers. METHODS: The general information, noise exposure and blood pressure were collected through questionnaires and physical examinations. Chi-square test was used to investigate the prevalence of hypertension under different cumulative noise exposure, and the effect of noise exposure and other factors on hypertension was analyzed by the restrictive cubic spline(RCS) combined with multivariatenon-condition Logistic regression model. RESULTS: The prevalence of hypertension in noise exposure group was higher than that in noise non-exposure group(P<0. 001). After adjusting for multiple factors, the restricted cubic spline model showed a dose-response relationship between cumulative noise exposure(CNE) and hypertension(overall correlation χ~2=75. 76, P<0. 001, and nonlinear χ~2=24. 17, P<0. 001). Compared with the steel workers exposure to lowest dose, the risk of hypertension of steel workers exposure to 82-94 and 95-107 dB(A) in group was 1. 81(95%CI 1. 31-2. 52) times and 2. 60(95%CI 1. 84-3. 68) times. CONCLUSION: There is a non-linear dose-response relationship between cumulative noise exposure and hypertension.

Transcriptomic profiling of human corneal epithelial cells exposed to airborne fine particulate matter (PM2.5).

PURPOSE: To explore the molecular mechanisms of PM2.5-induced dysfunction in human corneal epithelial cells (HCECs) and the potential role of the plasminogen activator inhibitor type-2 (PAI-2) in PM2.5-induced autophagy in vitro and in vivo. METHODS: RNA-Seq was performed to identify the differentially expressed genes (DEGs) in PM2.5-exposed HCECs compared to unexposed condition, followed by validation via real-time PCR (qRT-PCR). Corneal fluorescein staining and tear secretion were assessed in the PM2.5-exposed rat model. The expression of PAI-2 and autophagy-related markers were examined via immunoblotting, immunofluorescence staining and/or qRT-PCR in PM2.5-exposed or unexposed HCECs and rat corneas. PAI-2-knockdown HCECs were generated to study PAI-2's role in the PM2.5-induced autophagy in HCECs. RESULTS: A total of 434 DEGs-240 up-regulated and 194 down-regulated-were identified in PM2.5-exposed HCECs rather than unexposed HCECs. The expression of a few genes related to proliferation, inflammation, and aryl hydrocarbon stimulation were significantly altered by PM2.5 exposure. PAI-2 expression was up-regulated in PM2.5-exposed HCECs, sharing a similar fluctuation trend with autophagy-related markers LC3B II and BECN1 according to various exposure periods. Moreover, PAI-2 knockdown significantly suppressed the expression of LC3B and BECN1 in PM2.5-exposed HCECs. The corneal fluorescein staining was enhanced and tear secretion was significantly reduced in PM2.5-exposed rat eyes. PAI-2 expression was also increased in PM2.5-exposed rat corneas, together with the up-regulation of several autophagy-related markers. CONCLUSION: The present study identified the altered expression of hundreds of genes in PM2.5-exposed HCECs, which suggests the importance of PM2.5 for cornea health. The involvement of PAI-2 was discovered in the PM2.5-induced autophagy in HCECs as well as likely in rat corneas, which implied that PAI-2 may become a potential target of clinical treatment of PM2.5-associated ocular surface diseases.

Visual outcome and optical quality after implantation of zonal refractive multifocal and extended-range-of-vision IOLs: a prospective comparison.

PURPOSE: To compare the visual outcomes and optical quality of 2 presbyopia-correcting intraocular lenses (IOLs) with those of a monofocal IOL. SETTINGS: Eye Center, the Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, China. DESIGN: Prospective cohort study. METHODS: The study included patients who had cataract surgery and were implanted with a Tecnis Symfony Extended Range of Vision (EROV) IOL (ZXR00), a zonal refractive multifocal IOL (Lentis Comfort LS-313 MF15), or a monofocal IOL (Lentis L-313). Postoperative examinations took place at 1 week, 1 month, and 3 months and included visual acuity at far, intermediate, and near distances, defocus curves, contrast sensitivity, wavefront aberrations, and modulation transfer function (MTF). Patients completed the Visual Function Index questionnaire (VF-14), the Quality of Vision questionnaire (QoV), and a visual quality self-evaluation. RESULTS: One hundred thirteen patients were enrolled. The EROV and multifocal IOLs achieved a significantly better range of intermediate vergences (P < .05), better distance-corrected intermediate visual acuity (P ≤ .001), higher VF-14 (P < .05) and visual quality self-evaluation scores (P < .05) than the monofocal IOL, but there were no significant differences between the 2 presbyopia-correcting IOLs. The EROV provided lower total wavefront aberrations and better MTF than the multifocal and the monofocal IOLs (P < .05) but demonstrated a worse QoV score (P < .05), especially for severity of halo (P < .01) and starburst (P < .05) symptoms. CONCLUSIONS: Both the Tecnis Symfony ZXR00 and the Lentis Comfort LS-313 MF15 offered excellent visual restoration and stable distance and intermediate visual acuity, good subjective visual function, and good contrast sensitivity. The EROV IOL provided better objective optical quality and more prominent dysphotopsia symptoms than the multifocal IOL.

Comparison of Perioperative Parameters in Femtosecond Laser-Assisted Cataract Surgery Using 3 Nuclear Fragmentation Patterns.

PURPOSE: The purpose of this study was to compare the perioperative parameters of quadrant, sextant, and grid lens fragmentation patterns in femtosecond laser-assisted cataract surgery (FLACS). DESIGN: Prospective randomized clinical trial. METHODS: Setting: Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. STUDY POPULATION: A total of 894 eyes in 661 patients with cataracts were enrolled. Intervention or observation procedures: the nuclear density was graded according to the Emery-Little classification. Patients received lens fragmentation using a quadrant, sextant, or grid pattern after random allocation. Evaluations included intraoperative parameters, complications, and postoperative outcomes. MAIN OUTCOME MEASUREMENTS: effective phacoemulsification time (EPT), intraoperative complications, visual acuity and intraocular pressure at one day postoperatively, as well as endothelial cell density, endothelial cell loss, and central corneal thickness at 1 week postoperatively. RESULTS: In grade 1 nuclei, the mean EPT in the grid group was the shortest compared to those in the quadrant (P = 0.011) and sextant (P = 0.001) groups. In grade 2 nuclei, all 3 patterns showed no significant differences in the mean EPT (P > 0.05). In grade 3 nuclei, the sextant group revealed shorter mean EPT than the grid (P = 0.017) and quadrant (P > 0.05) groups. In grades 4 and 5 nuclei, the quadrant pattern had the shortest mean EPT among all 3 patterns (P < 0.05). The grid pattern is associated with higher intraocular pressure in hard nuclei (grades 4 and 5) than the other 2 patterns (P < 0.05). CONCLUSIONS: The grid and quadrant patterns allow for shorter EPT in soft (grade 1) and hard (grades 4 and 5) nuclei, respectively. All 3 patterns can be selected for treating grade 2 nuclei. The sextant pattern may be the best option when treating grade 3 nuclei. The grid pattern should be avoided in hard nuclei combined with glaucoma or glaucoma suspect.

Opacification of lentoid bodies derived from human induced pluripotent stem cells is accelerated by hydrogen peroxide and involves protein aggregation.

Despite the recent breakthrough in cataract drug development, further improvements have been limited by the lack of human in vitro cataract disease models. This study, therefore, aims to generate a qualified cataract disease model. Mature lentoid bodies (LBs) on Day 25 (D25), which were differentiated from human induced pluripotent stem cells (iPSCs) using the "fried egg" method, were continually culturing (control) or extra treated with either ultraviolet (UV) radiation or hydrogen peroxide (H2 O2 ). The LBs' shape alteration and opacity were examined using light microscopy and mean gray value evaluation. Their structure and crystallin expression were examined using immunofluorescence and transmission electron microscopy (TEM). Real-time polymerase chain reaction and western blot were used to investigate the potential role of autophagy in cloudy LBs. Mature LBs became cloudy with time which was accelerated by H2 O2 . Immunofluorescence examinations and TEM showed that the H2 O2 -treated and control LBs had similar shapes, lens capsule, and monolayer lens epithelial cell (LEC) structures. However, we were unable to do further assessment of the UV-treated LBs as the structures of LBs were easily damaged when treated with UV radiation. Cells containing aggregated protein (αA-crystallin and αB-crystallin) puncta were more abundant in the H2 O2 -treated LBs as compared with control LBs. Moreover, LC3B expression decreased with age in anterior lens capsules obtained from age-related cataracts (ARCs) patients as compared with LC3B levels in primary LECs, which is consistent with that LC3B expression in LBs was lower on D45 than on D25. Our study found that human iPSCs-derived LBs became cloudy with time which was accompanied by protein aggregation, and this phenomenon was accelerated by H2 O2 , suggesting that LBs with extending culture may serve as a human model for in vitro ARCs.

Cytokine profiling reveals increased serum inflammatory cytokines in idiopathic choroidal neovascularization.

BACKGROUND: The exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity. METHODS: This case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). RESULTS: Serum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area. CONCLUSION: Serum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV.

Bromfenac Inhibits TGF-ß1-Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts.

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown antifibrotic effects on several diseases. The aims of the present in vitro study were to investigate the antifibrotic effects of bromfenac (a kind of NSAID) on primary human pterygium fibroblasts (HPFs) and primary human conjunctival fibroblasts (HConFs), as well as to explore the possible mechanisms of these effects. Methods: The cells used in this study were primary HPFs and HConFs, and profibrotic activation was induced by transforming growth factor-beta1 (TGF-ß1). Western blot, quantitative real-time PCR, and immunofluorescence (IF) assays were used to detect the effects of TGF-ß1 and bromfenac on the synthesis of fibronectin (FN), type III collagen (COL3), and alpha-smooth muscle actin (α-SMA) in HPFs and HConFs; the changes of signaling pathways were detected by Western blot; cell migration ability was detected by wound healing assay; cell proliferation ability was detected by CCK-8 assay; and pharmaceutical inhibitions of the downstream signaling pathways of TGF-ß1 were used to assess their possible associations with the effects of bromfenac. Results: Bromfenac suppressed the TGF-ß1-induced protein expression of FN (0.59 ± 0.07 folds, P = 0.008), COL3 (0.48 ± 0.08 folds, P = 0.001), and α-SMA (0.61 ± 0.03 folds, P = 0.008) in HPFs. Bromfenac also attenuated TGF-ß1-induced cell migration (0.30 ± 0.07 folds, P < 0.001), cell proliferation (0.64 ± 0.03 folds, P = 0.002) and the expression levels of p-AKT (0.66 ± 0.08 folds, P = 0.032), p-ERK1/2 (0.69 ± 0.11 folds, P = 0.003), and p-GSK-3ß-S9 (0.65 ± 0.10 folds, P = 0.002) in HPFs. PI3K/AKT inhibitor (wortmannin) and MEK/ERK inhibitor (U0126) reduced the TGF-ß1-induced synthesis of FN, COL3, and α-SMA in HPFs. All the results were similar in HConFs. Conclusions: Bromfenac protects against TGF-ß1-induced synthesis of FN, α-SMA, and COL3 in HPFs and HConFs at least in part by inactivating the AKT and ERK pathways.

Impacts of air pollution on dry eye disease among residents in Hangzhou, China: A case-crossover study.

The purpose of this study is to investigate the potential associations between air pollution and dry eye disease (DED). Data of outdoor air pollutants and meteorology as well as outpatient visits for DED were collected. A time-stratified case-crossover approach was used to analyze the associations between ambient air pollutants and outpatient visits for DED. Among the 5062 DED patients studied, 65.45% were female and 34.55% were male. In the single-pollutant model, significant associations were observed between an increase of 10 µg/m3 in the concentrations of fine-particulate matter with a median aerometric diameter of less than 10 µm (PM10), fine-particulate matter with a median aerometric diameter of less than 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) and outpatient visits for DED. These results were consistent with those of the multipollutant model. The strongest associations between air pollutants and patient visits were observed during the cold season and in patients aged 21-40. The significant association between air pollutants (PM10, PM2.5, SO2, NO2, and CO) and DED outpatient visits indicates the importance of increased environmental protection.

A New Long Noncoding RNA ALB Regulates Autophagy by Enhancing the Transformation of LC3BI to LC3BII during Human Lens Development.

Autophagy is essential in lens organelle degradation. This study aimed to seek potential autophagy-associated long noncoding RNAs (lncRNAs) and their relative mechanisms in human lens development using the "fried egg" lentoid body (LB) generation system. The expression pattern of LC3B in differentiating LBs was similar to that in developing a mouse lens in vivo. Among the massive lncRNAs expressed with a significant difference between induced pluripotent stem cells (iPSCs) and LBs, lncRNA affecting LC3B (ALB), which was predicted to have a co-relationship with the autophagy marker LC3B, was highly expressed in differentiating lens fibers in LBs. This result was consistent with its high expression in human embryonic lenses compared to those in embryonic stem cells (ESCs). Furthermore, lncRNA ALB knockdown resulted in the downregulation of LC3BII at the protein level, therefore inhibiting the autophagy process in human lens epithelial cells (HLECs). Our results identify lncRNA ALB, a potential autophagy regulator in organelle degradation during human lens development, highlighting the importance of lncRNAs in lens development.

Air pollution and outpatient visits for conjunctivitis: A case-crossover study in Hangzhou, China.

BACKGROUND: Conjunctivitis, one of the most common ocular surface diseases, can be caused by many factors. OBJECTIVES: The objective of this study was to investigate the potential association between conjunctivitis and air pollutants. MATERIALS AND METHODS: Data of 9737 outpatient visits for conjunctivitis from July 1, 2014 to June 30, 2016 were obtained from the Eye Center of the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. The data were linked to data on the concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), and fine particulate matter with a median aerometric diameter of less than 10 and 2.5 µm (PM10 and PM2.5, respectively), which were obtained from the Environmental Protection Department of Zhejiang Province. A time-stratified case-crossover study design and conditional logistic regression were applied to analyze the association between air pollutants and outpatient visits for conjunctivitis. RESULTS: A 10 µg/m3 increase in PM10, PM2.5, SO2, NO2, and CO concentrations on the same day as the hospital visit or on lag days before the hospital visit date was associated with outpatient visits for conjunctivitis. The strongest association was observed between SO2 and conjunctivitis patients aged 2-5 years. Variation occurs between warm and cold seasons, between genders, and among different age groups. CONCLUSIONS: Our study provided evidence that outpatient visits for conjunctivitis were significantly associated with air pollution in Hangzhou, China.

Thermosensitive chitosan-based hydrogels releasing stromal cell derived factor-1 alpha recruit MSC for corneal epithelium regeneration.

Corneal epithelium integrity depends on continuous self-renewing of epithelium and connections between adjacent cells or between the cells and the basement membrane. Self-renewing epithelium cells mainly arise from the continuous proliferation and differentiation of the basal layer and limbal stem cells. The aim of the present study was to generate a bioactive, thermosensitive chitosan-gelatin hydrogel (CHI hydrogel) by incorporating exogenous recombinant human stromal cell-derived factor-1 alpha (SDF-1 alpha) for corneal epithelium regeneration. The exogenous SDF-1 alpha could enhance the stem cells proliferation, chemotaxis and migration, and the expression levels of related genes were significantly elevated in LESCs and mesenchymal stem cells (MSCs) in vitro. Moreover, the MSCs promoted the proliferation and maintained the corneal fate of the LESCs. The rat alkali injury model was used for in vivo study. The injured eyes were covered with CHI hydrogel alone or rhSDF-1 alpha-loaded CHI hydrogel. All rats were followed for 13days. Histological examination showed that the SDF-1 alpha/CHI hydrogel complex group had a nearly normal thickness; moreover, it was also found that this group could upregulate the expression of some genes and had more ΔNp63-positive cells. The SDF-1 alpha/CHI hydrogel complex group had a more tightly arranged epithelium compared with the control group using transmission electron microscopy (TEM). The mechanism for this may have involved the activation of stem cell homing and the secretion of growth factors via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could provide a new idea for the clinical application. STATEMENT OF SIGNIFICANCE: The clarity of cornea is important for normal vision. The loss or dysfunction of LESCs leads to the impairment of corneal epithelium. The complete regeneration of corneal epithelium has not been achieved. Our study demonstrated that the incorporation of rhSDF-1 alpha with CHI hydrogel accelerated corneal epithelium reconstruction with more native structural and functional properties. The mechanism may involve in inducing proliferation and migration of the LESCs and MSCs to the injury site via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could be a practical application for clinical therapy.

Airborne particulate matter (PM2.5) triggers autophagy in human corneal epithelial cell line.

PURPOSE: To investigate particulate matter (PM2.5)-induced damage to human corneal epithelial cells (HCECs) and to determine the underlying mechanisms. METHODS: HCECs were exposed to PM2.5 at a series of concentrations for various periods. Cell viability was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was evaluated via 5-ethynyl-2'-deoxyuridine (EdU) analysis, while autophagy was determined by immunofluorescence and Western blot. RESULTS: PM2.5-induced cell damage of HCECs occurred in a time- and dose-dependent manner. Decreased cell viability and proliferation as well as increased apoptosis were observed in HCECs after PM2.5 exposure for 24 h. Autophagy in HCECs was slightly inhibited in the early stage (before 4 h) of exposure but significantly activated in the late stage (after 24 h), as evidenced by a decrease in the former and increase in the latter of the expression of the autophagy-associated markers LC3B, ATG5, and BECN1. Interestingly, rapamycin, an autophagy activator, attenuated early-stage but aggravated late-stage PM2.5-induced cell damage, suggesting that the role of autophagy in HCECs may change over time during PM2.5 exposure. In addition, in the early stage, the expression of LC3B and ATG5 increased in cells co-treated with rapamycin and PM2.5 compared to rapamycin-only or PM2.5-only treated cells, suggesting that autophagy may benefit cell viability after PM2.5 exposure. CONCLUSIONS: The results indicate the potential role of autophagy in the treatment of PM2.5-induced ocular corneal diseases and provide direct evidence for the cytotoxicity, possibly involving an autophagic process, of PM2.5 in HCECs.