Effect of PPARγ on oxidative stress in diabetes-related dry eye.

Oxidative stress is closely associated with diabetes and can cause free radical accumulation and eventually lead to ocular surface tissue damage. The purpose of this study was to investigate peroxisome proliferator-activated receptor-γ (PPARγ) expression in the lacrimal gland (LG), meibomian gland, and cornea of diabetes-related dry eye mice and whether the PPARγ agonist rosiglitazone can alleviate the oxidative stress of the ocular surface, thereby improving the condition of diabetes-related dry eye. Quantitative RT-PCR (Q-PCR) showed that the PPARγ, catalase, glutathione peroxidase 3, and heme oxygenase-1 (HO-1) mRNA expression levels in the LG of diabetes-related dry eye mice decreased at 8 and 12 weeks. In addition, the increased levels of oxidative stress were confirmed by western blot. Although the mRNA expression levels of antioxidant enzymes in the cornea and meibomian gland decreased at 8 weeks, some of them recovered by 12 weeks. Rosiglitazone alleviated ocular surface damage and increased corneal sensitivity and tear production in diabetes-related dry eye mice. Moreover, the reactive oxygen species accumulation was reduced and the PPARγ, HO-1, and glutathione peroxidase 3 mRNA expression levels were increased in the LG. The PPARγ, HO-1, translocase of the outer membrane 20, and mitochondrial transcription factor A protein levels were also significantly increased. These results demonstrated that rosiglitazone reduced oxidative stress in the LG of diabetes-related dry eye mice, at least in part, by activating PPARγ to up-regulate antioxidant enzyme expression.

Clinical and in vivo confocal microscopy characteristics of Candida keratitis following keratoplasty.

BACKGROUND: We present six patients who developed Candida keratitis postoperatively. The clinical features, diagnostic testing including in vivo confocal microscopy, and outcomes are presented. METHODS: Six patients who developed Candida keratitis following penetrating and endothelial keratoplasty, were referred to Tianjin Medical University Eye Hospital between 2018 to 2021.The diagnosis was established following cultures of either corneal scraping or biopsy. In vivo confocal microscopy examination was also performed to confirm the diagnosis and characterize the morphology, distribution and the depth of Candida spp. All patients were treated with topical voriconazole (VCZ) 1% and natamycin (NTM) 5%. Patients with mid/deep stromal keratitis or interface infection were treated additionally with intrastromal or interface VCZ irrigation (0.05 mg/0.1mL). RESULTS: The cultures of corneal scrapings (4 cases) or biopsies (2 cases) were all positive for Candida spp. In vivo confocal microscopy examination was positive for fungal elements in five of the six patients. The infection resolved in five of the six patients. The patients' final uncorrected visual acuity (UCVA) ranged from hand movements (HM) to 20/80. CONCLUSION: In vivo confocal microscopy is a useful non-invasive clinical technique for confirming the diagnosis of Candida keratitis. Intrastromal and interface irrigated VCZ injections are effective treatment options.

Effect of preoperative pupil offset on corneal higher-order aberrations after femtosecond laser-assisted in situ keratomileusis.

BACKGROUND: This study aimed to investigate the relationship between multiple higher-order aberrations (HOAs) subgroups and pupil offset, as well as to analyze the factors affecting postoperative corneal HOAs in patients with different degrees of refractive errors. METHODS: We enrolled 160 patients (316 eyes) aged ≥ 18 years who had undergone femtosecond laser-assisted in situ keratomileusis (FS-LASIK) treatment. Based on the relationship between the preoperative pupil offset and the postoperative ΔHOAs, all patients were divided into two groups: group I (pupil offset ≤ 0.20 mm) and group II (pupil offset > 0.20 mm). All of the eyes had low to high myopia with or without astigmatism (manifest refraction spherical equivalent (MRSE) < -10.00 D). Uncorrected distance visual acuity, corrected distance visual acuity, MRSE, pupil offset, central corneal thickness, corneal HOAs, vertical coma (Z3-1), horizontal coma (Z31), spherical aberration (Z40), trefoil 0° (Z33), and trefoil 30° (Z3-3) over a 6 mm diameter central corneal zone diameter were evaluated preoperatively and at 1 and 3 months postoperatively. RESULTS: Our result revealed significant differences in postoperative corneal total root mean square (RMS) HOAs, RMS vertical coma, RMS horizontal coma, RMS spherical aberration, and RMS trefoil 30° between group I and group II. ΔMRSE was found to be an effective factor for ΔRMS HOAs (R2 = 0.383), ΔRMS horizontal coma (R2 = 0.205), and ΔRMS spherical aberration (R2 = 0.397). In group II, multiple linear regression analysis revealed a significant correlation between preoperative pupillary offset and Δtotal RMS HOAs (R2 = 0.461), ΔRMS horizontal coma (R2 = 0.040), and ΔRMS trefoil 30°(R2 = 0.089). The ΔRMS vertical coma effect factor is the Y-component, and the factor influencing ΔRMS spherical aberration was ΔMRSE (R2 = 0.256). CONCLUSION: A small pupil offset was associated with a lower induction of postoperative corneal HOAs. Efforts to optimize centration are critical for improving surgical outcomes in patients with FS-LASIK.

Safety and Efficacy of the Phototherapeutic Keratectomy for Treatment of Recurrent Corneal Erosions: A Systematic Review and Meta-Analysis.

BACKGROUND: Phototherapeutic keratectomy (PTK) has been increasingly used to treat severe recurrent corneal erosion syndrome (RCES) patients who do not respond to other treatments. However, the efficacy and complication of each study are currently uncertain due to varying rates. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of the PTK for recurrent corneal erosions. METHODS: This article performed a systematic literature research in Cochrane, Embase, PubMed, Scopus, and the Web of Science for the literature on PTK treatment of RCES until December 20, 2022. The extracted data including recurrence rate and the adverse event rate were used for meta-analysis. RESULTS: The recurrence rate was 18% (95% CI, 13%-24%) (129/700 eyes). Subgroup analysis showed that the RCE recurrence was 17% (95% CI, 9%-24%) after trauma and 22% (95% CI, 11%-32%) in the corneal dystrophy group. Treatment-related adverse events included subepithelial haze, hyperopic shift, and decrease of the best spectacle-corrected visual acuity. In this study, the incidence of these events was 13% (95% CI, 6%-21%), 20% (95% CI, 11%-28%), and 11% (95% CI, 5%-16%), respectively. CONCLUSIONS: PTK represented a valuable treatment option for patients with recurrent corneal erosions, especially those with traumatic injuries, which had minimal side effects.

Efficacy and Safety evaluation of a single thermal pulsation system treatment (Lipiflow®) on meibomian gland dysfunction: a randomized controlled clinical trial.

PURPOSE: Evaluate the efficacy and safety of LipiFlow® thermal pulsation treatment system compared with lid massage combined warm compress in Chinese patients with meibomian gland dysfunction (MGD). METHODS: Patients (n = 100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n = 50 eyes) received a single LipiFlow® thermal pulsation system treatment. In warm compress group, patients (n = 50 eyes) underwent warm compress daily for two weeks after an initial manual lid massage. Patients' symptoms were evaluated using Standard Patient Evaluation for Eye Dryness (SPEED) questionnaire. Safety parameters included best-corrected visual acuity (BCVA), intraocular pressure (IOP) and objective parameters including meibomian glands yielding lipid secretion (MGYLS) number, meibomian glands secretion (MGS) score, lipid layer thickness (LLT), tear-film breakup time (TBUT), corneal fluorescein staining (CFS) were measured and presented from baseline and to 3 months post-treatment. RESULTS: Baseline parameters in both groups were comparable (p > 0.05). SPEED score and TBUT improved in two groups from baseline to 3 months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3 months. CFS showed significant improvement in warm compress group at 1 month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number. CONCLUSION: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3 months.

The correlation between Demodex infestation and meibomian gland dysfunction at different ages.

BACKGROUND: This study aimed to explore the associations between Demodex infestation and the ocular surface characteristics of meibomian gland dysfunction (MGD) in different age groups, to further understand the effect of Demodex on MGD. METHODS: A total of 202 consecutive MGD patients aged 18 to 70 years were randomly recruited. All patients were divided into two groups based on their age: young patients (18-40 years) and elderly patients (41-70 years). The main observations were the different relationship between Demodex infestation and ocular surface and meibomian gland (MG) parameters in two age groups. We also compared ocular surface and MG parameters between the young and the elderly groups. Demodex infestation was diagnosed based on expert consensus in China. RESULTS: Our results indicated significant differences among young Demodex-positive, suspicious-positive, and negative patients in MG dropout (P = 0.000), plugging of MG orifices (P = 0.000), lid margin abnormality (P = 0.000), and meibum quality (P = 0.000). In elderly patients, there were significant differences among the Demodex-positive, suspicious-positive, and negative groups in terms of ocular surface disease index (OSDI) (P = 0.037), fluorescein tear film break-up time (FBUT) (P = 0.002), corneal fluorescein staining (CFS) (P = 0.036), MG dropout (P = 0.000), plugging of MG orifices (P = 0.008), lid margin abnormality (P = 0.000), and MG expression (P = 0.037). The mean number of mites in elderly Demodex-positive patients (10.64 ± 7.50) was greater than that of in young patients (7.60 ± 4.71) (P = 0.014). MG dropout (P = 0.000), plugging of MG orifices (P = 0.006), lid margin abnormality (P = 0.000), MG expression(P = 0.001), and meibum quality (P = 0.032) were more severe in elderly Demodex-positive patients. Additionally, FBUT (P = 0.005) was lower and tear film lipid layer thickness (LLT) (P = 0.001) was higher in the elderly. CONCLUSION: The effect of Demodex infestation on the ocular surface and MG parameters of MGD was different in patients of different ages. It is necessary to pay more attention to the diagnosis and treatment of Demodex infestation in MGD.

Clinical observations of EVO-ICL implantation and changes in corneal astigmatism using a modified technique.

BACKGROUND: Implantable collamer lens (ICL) surgery techniques are constantly progressing. The purpose of this study was to investigate the application effect of the modified technique and its impact on the change in corneal astigmatism in EVO-ICL surgery. METHODS: The analysis of retrospective cohort data included 153 eyes of 81 patients with myopia from July 2018 to May 2020. An EVO-ICL was inserted by modified surgical skills, including a single 3.0 mm corneal incision and no ophthalmic viscosurgical device (OVD) before the insertion of the ICL (modified technique group: 41 cases, 80 eyes) and standard procedure (standard technique group: 40 cases, 73 eyes). Early postoperative intraocular pressure (IOP) was monitored at 2 and 24 h. IOP, corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), vault, and anterior chamber depth (ACD) were measured 1, 6, and 12 months following the initial examination. The corneal endothelial cell density (ECD) was monitored at 6 and 12 months after the operation. Surgically induced astigmatism (SIA) in the total, anterior, and posterior corneal surfaces was analysed 1 month after the operation. RESULTS: No serious complications were detected. The two groups had no difference in visual outcomes, ICL vaults, or ACD at any time point (P > 0.05). Two hours postoperatively, IOP was significantly lower in the modified technique group (16.22 ± 2.22 vs. 18.37 ± 1.92 mmHg, P < 0.05) than in the standard technique group. IOP decreased gradually after 24 h to preoperative levels. The postoperative IOP remained stable over a 12-month period. The ECD at 6 and 12 months was not significantly different between the groups (P > 0.05). SIA in the total, anterior, and posterior corneal surfaces were assumed to have no clinically meaningful differences between groups at one month after operation (P > 0.05). CONCLUSIONS: The modified technique is efficient and safe, producing comparable visual and structural outcomes without adversely affecting ECD, and reduces fluctuations in IOP at the early postoperative stages. The auxiliary incision in the standard technique does not increase corneal SIA, which is also a factor to consider for inexperienced surgeons.

Changes in asphericity of anterior and posterior corneal surfaces for mild-moderate and high myopia after topography-guided FS-LASIK.

PURPOSE: To compare changes in asphericity of anterior and posterior corneal surfaces for different myopia patients after corneal topography-guided femtosecond-assisted laser in situ keratomileuses (FS-LASIK), and to analyze correlations between asphericity of corneal surfaces and preoperative spherical equivalence (SEQ). METHODS: In this prospective study, 59 patients who underwent corneal topography-guided FS-LASIK surgery were enrolled and divided into the mild-moderate myopia group (67 eyes) and the high myopia group (44 eyes). Postoperative follow-ups were performed at 1, 3, and 6 months. Postoperative changes in aspherical coefficient (Q values), corneal higher-order aberrations (HOAs), and spherical aberrations (Z40) were compared between the two groups. Relevance between Q value changes and SEQ, HOAs, and Z40 as well as between SEQ and changes of HOAs and Z40 was analyzed. RESULTS: There was a significant increase in Q values of the anterior (each diameter) and posterior (6-8 mm) corneal surface in both groups than before surgery (P < 0.001). Q values of corneal anterior (each diameter) and posterior (7-9 mm) surface in the high group were considerably larger than the mild-moderate group (P < 0.05). Corneal anterior surface HOAs and Z40 values in the high group largely exceeded those of the mild-moderate group (P < 0.001). The preoperative SEQ was linearly correlated with postoperative anterior Q change (ΔQ), HOAs change (ΔHOAs), and spherical aberration change (ΔZ40). CONCLUSION: The changes of corneal asphericity in patients with high myopia were greater than mild-moderate myopia, with more corneal HOAs and Z40 introduced when corneal topography-guided FS-LASIK was conducted.

N-acetylcysteine alleviates ocular surface damage in STZ-induced diabetic mice by inhibiting the ROS/NLRP3/Caspase-1/IL-1ß signaling pathway.

Diabetes mellitus (DM) induces damage to the ocular surface, which leads to vision decline. In the current study, we investigated whether N-acetylcysteine (NAC) plays a protective role in diabetes-induced ocular surface damage. The diabetic mice model was treated with 0.3% NAC topically. Corneal epithelial integrity, tear volume and corneal sensitivity were examined by sodium fluorescein staining, phenol red cotton thread and esthesiometer respectively. The level of reactive oxygen species (ROS) was measured with 2',7-dichlorofluorescein diacetate. The expression of NLRP3, IL-1ß and caspase-1 were evaluated by RT-PCR, western blot and immunostaining. The level of SOD1 was assessed by RT-PCR. We found that the expression of NLRP3, IL-1ß and caspase-1 were elevated in diabetic cornea and conjunctiva. Treatment with NAC improved corneal epithelial integrity, increased tear production and corneal sensitivity in diabetic mice. Moreover, NAC markedly attenuated ROS accumulation and decreased NLRP3, IL-1ß and caspase-1 levels in diabetic cornea and conjunctiva. These results suggest that NAC improves ocular surface damage in STZ-induced diabetic mice, which may be related to the inhibition of the ROS/NLRP3/Caspase-1/IL-1ß signaling pathway.

α-MSH ameliorates corneal surface dysfunction in scopolamine-induced dry eye rats and human corneal epithelial cells via enhancing EGFR expression.

Dry eye (DE) is a chronic, multifactorial ocular surface disease associated with visual disturbance, tear film instability, hyperosmolarity, ocular surface inflammation and damage. Effective intervention is necessary to control this disease. In this study we topically applied α-melanocyte stimulating hormone (α-MSH) on the ocular surface of scopolamine-induced DE rats and found that it promoted tear secretion, reduced tear breakup time and fluorescein sodium staining and increased the number of conjunctival goblet cells. To investigate the mechanism, protein array was conducted, which showed that α-MSH exerted its effects via epithelial growth factor receptor (EGFR) in the JAK-STAT signaling pathway. Furthermore, in vitro experiments showed that α-MSH protected human corneal epithelial cells (hCECs) by maintaining their migration ability and viability and decreasing apoptosis. However, blockade of EGFR abolished these protective effects. Moreover, α-MSH decreased the level of autophagy in benzalkonium chloride (BAC)-stressed hCECs via EGFR. These results demonstrated that α-MSH ameliorated lesions and restored ocular surface functions by upregulating EGFR expression.

Refractive errors and risk factors for myopia in infants aged 1-18 months in Tianjin, China.

BACKGROUND: Infancy is the of a child's visual development. Refractive errors, especially myopia, are a common vision disorder. Thus, the purpose of this study was to explore refractive errors and risk factors for myopia among infants aged 1-18 months in Tianjin, China. METHODS: A total of 583 infants aged 1-18 months participated in this cross-sectional study at Tianjin Women's and Children's Health Center in China from February 2019 to November 2020. Each infant received a complete ophthalmologic examination, and myopia-related risk factors were investigated using a questionnaire. RESULTS: A total of 583 eligible infants participated in this study, including 312 (53.5%) boys and 271 (46.5%) girls. There were 164 (28.1%) premature born infants. The mean age was 6.59 ± 4.84 months (range, 1-18 months). The mean spherical equivalent (MSE) for the right eye was 1.81 D ± 1.56 D, with no difference related to sex (P = 0.104). Refractive state showed an average hyperopia of +2.74 ± 1.74 D at early ages, followed by a trend toward less hyperopia, finally reaching +1.35 ± 1.44 D at the age of 18 months (P ≤0.001). The overall prevalence rates of myopia (MSE ≤ -0.50 D), emmetropia (-0.50 D

Comparison of parameter agreement for characterization of corneal subbasal nerve plexus in the whorl-like region and central cornea using in vivo confocal microscopy.

PURPOSE: To compare the reliability of the whorl-like region with that of the central cornea for accurate assessment of corneal subbasal nerve plexus (SNP) by analyzing the parameter variability of these two anatomical regions in repeated measurements. METHODS: Participants were scanned in the central cornea and whorl-like region with in vivo confocal microscopy on three occasions by two examiners within a time span of one week. Coefficients of repeatability (CoR), intra-class correlation coefficient (ICC), and Bland-Altman scatter plots with 95% limits of agreement (LOA) in the central cornea and whorl-like region were calculated, respectively, based on the nerve fiber length, then the inter-observer and intra-observer agreement were compared between these two anatomical regions. RESULTS: The inter-observer ICC was 0.945, the inter-observer CoR was 0.052, the intra-observer ICC was 0.936, and the inter-observer CoR was 0.046, with narrow 95% LOA within 1 standard deviation in the whorl-like region, whereas the inter-observer ICC was 0.600, the inter-observer CoR was 0.207, the intra-observer ICC was 0.206, and the intra-observer CoR was 0.253, with 95% LOA nearly threefold wider than the standard deviation in the central cornea. CONCLUSIONS: Nerve parameter in the whorl-like region showed higher inter-observer and intra-observer agreement than that of the central cornea. The whorl-like region is a more reliable site for accurate assessment of SNP.

SP1-mediated lncRNA PVT1 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract via miR-214-3p/MMP2 axis.

Emerging evidence illustrates the critical roles of long non-coding RNAs (lncRNAs) in the diabetes. However, the deepgoing regulation of lncRNA PVT1 in the diabetic cataract (DC) is still unclear. Here, present research investigates the pathologic roles and underlying mechanism by which lncRNA PVT1 regulates the DC pathogenesis. Human lens epithelial (HLE) B-3 cells were induced by the high glucose (HG) to simulate the DC microenvironment models. Results revealed that lncRNA PVT1 expression was up-regulated in the HG-induced HLE B-3 cells as compared to the normal glucose group. Transcription factor SP1 could bind with the promoter region of PVT1 and activate its transcription. Functionally, PVT1 knock-down could repress the proliferation and promote the apoptosis of HLE B-3 cells. Mechanistically, PVT1 acted as the 'miRNA sponge' to target miR-214-3p/MMP2 axis. This finding revealed a novel insight of lncRNA PVT1 for the DC pathogenesis, providing an inspiration for the DC mechanism.

Inflammation and oxidative stress induced by lipid peroxidation metabolite 4-hydroxynonenal in human corneal epithelial cells.

PURPOSE: Oxidative stress is widely known to be a major contributor in the pathogenesis of dry eye disease (DED). 4-Hydroxynonenal (4-HNE), a well-known byproduct frequently measured as an indicator of oxidative stress-induced lipid peroxidation, has been shown to be elevated in both human and murine corneal DED samples. This study aims to investigate if 4-HNE is responsible for the oxidative stress in human corneal epithelial cells (HCECs) and explores the underlying mechanism by which it confers its effects. METHODS: SV40-immortalized HCECs were cultured in minimum essential media (MEM) with 1% penicillin/streptomycin and 10% fetal bovine serum. HCECs were exposed to media with or without 4-HNE and cell culture supernatants were collected at 4 and 24 h. Cellular reactive oxygen species (ROS) measurement was performed using a 2',7'-dichlorofluorescein diacetate (DCFDA) assay kit according to the manufacturer's instructions. Protein levels of antioxidant enzymes copper/zinc superoxide dismutase 1 (SOD1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were analyzed by Western blot. NF-κB activation and expression of IL-6 and IL-8 were measured using an NF-κB p65 Total SimpleStep ELISA Kit and Proteome Profiler Human Cytokine Array Kit. Cell viability was evaluated by LDH cytotoxicity assay. RESULTS: Treatment with 4-HNE decreased cell viability of HCECs. Band intensities corresponding to levels of ROS production showed a significant increase in ROS generation after treatment with 4-HNE. 4-HNE decreased SOD1 levels and upregulated NQO1 expression in HCECs. A significant increase in activation of NF-κB and production of pro-inflammatory cytokines IL-6 and IL-8 was observed after treatment with 4-HNE. Exposure to N-acetylcysteine (NAC), an antioxidant and ROS scavenger, antagonized the oxidative effects of 4-HNE on HCECs. CONCLUSION: 4-HNE induces oxidative stress in corneal epithelial cells by increasing levels of ROS generation and modifying the expression of antioxidant enzyme levels, decreasing cell viability of HCECs in vitro. This study demonstrates a potential pathway by which 4-HNE functions to confer its detrimental effects and provides a new therapeutic target for the treatment of DED.

Evaluation of tear film and the morphological changes of meibomian glands in young Asian soft contact lens wearers and non-wearers.

BACKGROUND: The aim of this study was to explore the differences in terms of tear film and meibomian glands (MGs) between young Asian soft contact lens (CL) wearers and non-wearers. METHODS: A prospective, cross-sectional observational study was conducted using 148 subjects (63 non-wearers, and 85 soft CL wearers who had been wearing CLs for more than 1 year) recruited from a clinic in Tianjin, China. All subjects first responded to an Ocular Surface Disease Index (OSDI) questionnaire and then underwent a standardized dry eye examination, which included measuring tear meniscus height (TMH), non-invasive tear breakup time (NIBUT), and corneal fluorescein staining (CFS). The MGs were evaluated via ImageJ, distorted MG count and the MG dropout were recorded. RESULTS: Compared to the control group (non-wearers), the CL group recorded higher OSDI and CFS scores, lower TMH and NITBUT values, a larger distorted MG count, and larger MG dropout (all P < 0.05). Pearson correlation analysis found a correlation between MG dropout and the duration of CL use (r = 0.440, P < 0.001), OSDI (r = 0.298, P = 0.006), and CFS scores (r = 0.442, P < 0.001). CONCLUSION: CL wearers showed higher MG dropout and reduced TMH and NITBUT, which likely contributes to severe CL-related dry eye symptoms. CL use may lead to a higher MG dropout rate, and the extent of the MG dropout presumably influences the tear film status in CL wearers.

Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling.

BACKGROUNDS/AIMS: To explore whether NLRP3 is involved in the development of cataract and to study the effect of NLRP3 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells. METHODS: Oxidative stress-induced apoptosis model was constructed by treating HLEB3 cells with 50 µM H2O2 at different times (6 h, 12 h) and was confirmed by flow cytometry and Western blot. HLEB3 were divided into NC, NC+H2O2, shNLRP3, and shNLRP3+H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, DCFH-DA to measure reactive oxygen species production, and Annexin V-FITC/PI staining to determine cell apoptosis. RESULTS: NLRP3 expression significantly increased in H2O2-induced HLEB3 cells. shRNA interference of NLRP3 inflammasome protects HLEB3 cells against oxidative stress-induced apoptosis by decreasing the expression levels of caspase-3 and Bax and increasing Bcl-2 expression. shNLRP3 was able to effectively suppress H2O2-induced apoptosis via inhibition of NF-κB signaling. CONCLUSION: NLRP3 might be involved in the apoptosis of lens epithelial cells. The inhibition of NLRP3 obviously attenuated H2O2-induced oxidative stress injury of human lens epithelial cells via NF-κB signaling.

Zidovudine protects hyperosmolarity-stressed human corneal epithelial cells via antioxidant pathway.

Dry Eye Disease (DED) is a very common disorder that can result in severe disability and vision loss. Although the pathogenesis of DED is not fully understood, hyperosmolarity, inflammation, and tear film instability are recognized as hallmarks of DED. Recently, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a class of medication used to treat HIV, have been shown to inhibit inflammation in a mouse model of retinal atrophy. In this study, we investigated whether Zidovudine (AZT) can inhibit human corneal epithelial cell (HCEC) inflammatory responses under hyperosmotic conditions. HCECs were cultured in hyperosmotic media containing AZT. Cell viability, cytokine production, and reactive oxygen species (ROS) production were measured. We found that AZT decreased nuclear factor kappa B (NF-κB) and Interleukin-6 (IL-6) levels, increased Superoxide Dismutase 1 (SOD1) production, decreased ROS production, and increased cell viability. These results support the novel use of AZT in the reduction of ocular surface inflammation and the promotion of corneal health in the context of DED.

The effects of local administration of mesenchymal stem cells on rat corneal allograft rejection.

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to promote long-term cellular and organ transplant acceptance due to their immunotherapeutic characteristics. Previous work from our lab using a rat allograft model has shown that systemic infusion of MSCs inhibited corneal allograft rejection and prolonged graft survival. Here, we further investigated the effects of local MSCs administration in the same animal model. METHODS: Donor-derived MSCs were isolated and cultured while corneal grafts obtained from Wistar rats were transplanted into Lewis rat hosts. Hosts were then randomly separated into four groups and treated with previously cultured MSCs at different times and doses. Graft survival was clinically assessed using slit-lamp biomicroscopy and the median survival time (MST) was calculated. Grafts were examined histologically using hematoxylin-eosin (H-E) staining and immunohistochemically using antibodies against CD4. A comprehensive graft analysis of IL-2, IL-4, IL-10, and IFN-γ expression was also conducted using both real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Postoperative MSCs injection prolonged graft survival time when compared with controls (MST 9.8 ± 1.2 days). Injection twice of MSCs (MST 12.6 ± 1.4 days) was more effective than a single injection (MST 10.8 ± 1.3 days). MSCs-treated groups also showed suppression of inflammatory cell as well as CD4 + T cell infiltration in the allograft region. IL-4 and IL-10 levels were significantly increased in grafts obtained from postoperative twice MSCs-treated rats when compared with controls. There were no significant differences in IL-2 or IFN-γ expression across groups. CONCLUSIONS: Subconjunctival injection of MSCs in rats was effective in prolonging corneal allograft survival. This effect was mediated by inhibition of inflammatory and immune responses, indicating an anti-inflammatory shift in the balance of T helper (Th)1 to T helper(Th) 2.

Intraocular myofibroblastoma in an infant: a case report.

BACKGROUND: Myofibroblastoma is a benign tumor composed of spindle cells and bands of hyalinized collagen. Intraocular myofibroblastoma in infancy is rarely encountered. CASE PRESENTATION: The present study reports the case of a 4-month-old female baby with intraocular myofibroblastoma. She was suspected as corneal perforation due to the rupture of a corneal neoplasm in the right eye. The anterior segment was also involved according to the Color Doppler ultrasonography. A surgical exploration was performed and the protuberant part of the mass was resected. Conventional HE staining showed numerous spindle-shaped cells with bands of collagen beneath multilayers of well-differentiated corneal epithelia. Immunohistochemical staining demonstrated the tumor cells were strong positive for vimentin and smooth muscle actin, while negative for S-100 protein. The mass was confirmed as myofibroblastoma. After 12 month follow-up, there was no apparent growth of the tumor. CONCLUSIONS: Myofibroblastoma is a very rare type of intraocular neoplasm, which may have complicated manifestation and could be misdiagnosed as dermoid or Peter's anomaly. Histopathological and immunohistochemical staining is crucial to form a precise diagnosis.

[Expression and function of microRNAs in the cornea].

MicroRNAs (miRNAs) are a class of small (21-2i nucleotictes), single-stranded, noncoding RNA molecules that regulate gene expression at the post-transcriptional or translational level by binding to the 3'-untranslated region of the target mRNAs. miRNAs ubiquitously exist in the genome of an organism. More than two hundred miRNA species are expressed in the eye, of which 25% are found in the cornea. miRNAs play important roles in corneal development, differentiation, glycogen metabolism, post-injury regeneration, and maintenance of homeostasis. On the other hand, miRNAs are involved in the regulation of pathological processes in the cornea, such as keratoconus, corneal neovascularization caused by corneal transplantation, herpes simplex virus infection and alkali burns. Therefore, miRNAs are expressed in a tissue-specific manner and regulate physiological and pathological processes in the cornea. The study of miRNA expression and regulation in the cornea would provide a theoretical basis for exploring pathogenic mechanisms and novel therapeutic targets for corneal diseases.