Presbyopia-Correcting Intraocular Lenses Implantation in Eyes After Corneal Refractive Laser Surgery: A Meta-Analysis and Systematic Review.

Purpose: To assess the efficacy, safety, and predictability of presbyopia-correcting intraocular lenses (IOLs) in cataract patients with previous corneal refractive surgery. Methods: A systematic literature search was performed to identify studies evaluating the clinical outcomes of presbyopia-correcting IOLs implantation in cataract surgery after laser refractive surgery. Outcomes were efficacy, safety and predictability parameters. Results: The authors identified 13 studies, involving a total of 128 patients and 445 eyes. Presbyopia-correcting IOLs were effective at improving distance, intermediate and near visual acuity aftercataract surgery. The proportion of post-laser surgery eyes with uncorrected distance visual acuity (UDVA) ≥ 20/25 was 0.82 [95% confidence interval (CI), 0.74-0.90] and the pooled rates of spectacle independence at near, intermediate, and far distances were 0.98 (95% CI, 0.94-1.00), 0.99 (95% CI, 0.95-1.00) and 0.78 (95% CI, 0.65-0.94) respectively. The percentage of participants who suffered from halos and glare was 0.40 (95% CI, 0.25-0.64) and 0.31 (95% CI, 0.16-0.60), respectively. The predictability had a percentage of 0.66 (95% CI, 0.57-0.75) and 0.90 (95% CI, 0.85-0.96) of eyes within ±0.5 diopters (D) and ±1.0 D from the targeted spherical equivalent. Conclusions: Presbyopia-correcting IOLs provide satisfactory results in terms of efficacy, safety and predictability in patients with previous corneal refractive surgery, but have a higher risk of photopic side effects such as halos and glare.

Lens Opacities Classification System III-based artificial intelligence program for automatic cataract grading.

PURPOSE: To establish and validate an artificial intelligence (AI)-assisted automatic cataract grading program based on the Lens Opacities Classification System III (LOCS III). SETTING: Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China. DESIGN: AI training. METHODS: Advanced deep-learning algorithms, including Faster R-CNN and ResNet, were applied to the localization and analysis of the region of interest. An internal dataset from the EENT Hospital of Fudan University and an external dataset from the Pujiang Eye Study were used for AI training, validation, and testing. The datasets were automatically labeled on the AI platform regarding the capture mode and cataract grading based on the LOCS III. RESULTS: The AI program showed reliable capture mode recognition, grading, and referral capability for nuclear and cortical cataract grading. In the internal and external datasets, 99.4% and 100% of automatic nuclear grading, respectively, had an absolute prediction error of ≤1.0, with a satisfactory referral capability (area under the curve [AUC]: 0.983 for the internal dataset; 0.977 for the external dataset); 75.0% (internal dataset) and 93.5% (external dataset) of the automatic cortical grades had an absolute prediction error of ≤1.0, with AUCs of 0.855 and 0.795 for referral, respectively. Good consistency was observed between automatic and manual grading when both nuclear and cortical cataracts were evaluated. However, automatic grading of posterior subcapsular cataracts was impractical. CONCLUSIONS: The AI program proposed in this study showed robust grading and diagnostic performance for both nuclear and cortical cataracts, based on LOCS III.

Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer's Disease in Amyloid Precursor Protein/Presenilin 1 Mice.

Increasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer's disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD within the inflammatory aspect. The hippocampus of CP model mice and controls were collected, and changes in protein expression were evaluated using two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis combined with liquid chromatography tandem mass spectrometry. A total of 15 differentially expressed proteins were identified in CP model mice, as compared with the controls. Among them, S100-A9, transthyretin, Cofilin 2, peroxiredoxin 2, and lipocalin-2 were validated by Western blot according to their dual function both in inflammation and AD. Based on 2D-DIGE analysis, CP animal model had higher levels of S100-A9, Cofilin 2, peroxiredoxin 2, and lipocalin-2 compared to controls. The level of Cofilin 2, one of the well-established proteins in the pathology of AD, was strongly correlated with the time course of CP pathology, indicating a specific molecular correlation between CP and AD. Moreover, the in vivo results showed the level of Cofilin 2 increased significantly along with a prominent increase of the phosphorylation of protein phosphatase 2 (PP2A) and tau protein in the cell lysates of Porphyromonas gingivalis (P.g-LPS)-treated SK-N-SH APPwt cells. Cofilin 2 inhibition resulted in a sharp decrease in PP2A dependent of tau phosphorylation. Furthermore, tumor growth factor (TGF)-ß1 was one of the most important inflammatory cytokines for the Pg-LPS-induced Cofilin 2 upregulation in SK-N-SH APPwt cells. These results showed inflammation served as the bond between CP and AD, whereas inflammatory related proteins could be the key linkers between the two diseases. Determining the association between CP and AD at the molecular mechanism will not only hold the direct evidence of the association between the two diseases but also provide a new way of preventing and treating AD: the effective prevention and treatment of CP could serve as a useful method to alleviate the development of AD.

Conjunctival Microbiota in Patients With Type 2 Diabetes Mellitus and Influences of Perioperative Use of Topical Levofloxacin in Ocular Surgery.

Background: Patients with type 2 diabetes mellitus (T2DM) are prone to ocular surface infections. We therefore characterized the conjunctival microbiome of T2DM patients and the influence of topical levofloxacin to investigate whether a dysbiosis is associated with this phenomenon. Methods: Conjunctival microbiome of 79 T2DM patients and 113 non-diabetic controls was profiled using the 16S rDNA sequencing approach. Furthermore, 21 T2DM and 14 non-diabetic patients who underwent cataract surgeries were followed up perioperatively and the influence of pre- and post-operative levofloxacin on the conjunctival microbiome was further investigated prospectively and compared longitudinally. Results: The α-diversity of the conjunctival microbiota was significantly higher in T2DM patients than in controls (P < 0.05). Significant differences in both composition and function of the conjunctival microbiome were identified on the ocular surface of T2DM patients as compared to non-diabetic controls. Particularly, phylum Bacteroidetes and Fusobacteria, genus Pseudomonas, Haemophilus, and Empedobacter were enriched, while genus Streptococcus was reduced on the T2DM ocular surface. Microbial genes functioning of bacterial chemotaxis was elevated in the conjunctival microbiome of T2DM patients. Furthermore, compared to the initial status, several genera including Staphylococcus were more abundant in the conjunctival microbiome of T2DM patients after 3-days use of preoperative levofloxacin topically, while no genus was more abundant in the non-diabetic follow-up group. No difference was observed between initial status and 7 days after ceasing all postoperative medications in both diabetic and non-diabetic follow-up groups. Conclusions: The conjunctival microbiome of T2DM patients was more complex and may respond differently to topical antibiotics.

Variants of WNT7A and GPR124 are associated with hemorrhagic transformation following intravenous thrombolysis in ischemic stroke.

AIMS: The canonical Wnt signaling pathway plays an essential role in blood-brain barrier integrity and intracerebral hemorrhage in preclinical stroke models. Here, we sought to explore the association between canonical Wnt signaling and hemorrhagic transformation (HT) following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients as well as to determine the underlying cellular mechanisms. METHODS: 355 consecutive AIS patients receiving IVT were included. Blood samples were collected on admission, and HT was detected at 24 hours after IVT. 117 single-nucleotide polymorphisms (SNPs) of 28 Wnt signaling genes and exon sequences of 4 core cerebrovascular Wnt signaling components (GPR124, RECK, FZD4, and CTNNB1) were determined using a customized sequencing chip. The impact of identified genetic variants was further studied in HEK 293T cells using cellular and biochemical assays. RESULTS: During the study period, 80 patients experienced HT with 27 parenchymal hematoma (PH). Compared to the non-PH patients, WNT7A SNPs (rs2163910, P = .001, OR 2.727; rs1124480, P = .002, OR 2.404) and GPR124 SNPs (rs61738775, P = .012, OR 4.883; rs146016051, P < .001, OR 7.607; rs75336000, P = .044, OR 2.503) were selectively enriched in the PH patients. Interestingly, a missense variant of GPR124 (rs75336000, c.3587G>A) identified in the PH patients resulted in a single amino acid alteration (p.Cys1196Tyr) in the intracellular domain of GPR124. This variant substantially reduced the activity of WNT7B-induced canonical Wnt signaling by decreasing the ability of GPR124 to recruit cytoplasmic DVL1 to the cellular membrane. CONCLUSION: Variants of WNT7A and GPR124 are associated with increased risk of PH in patients with AIS after intravenous thrombolysis, likely through regulating the activity of canonical Wnt signaling.

Comparison of the rotational stability between plate-haptic toric and C-loop haptic toric IOLs in myopic eyes.

PURPOSE: To compare the rotational stability of a plate-haptic toric intraocular lens (IOL) vs a C-loop haptic toric IOL in myopic cataract eyes. SETTING: Eye and Ear, Nose, and Throat Hospital of Fudan University, China. DESIGN: Prospective, randomized, controlled study. METHODS: Cataract eyes with axial length (AL) more than 24.5 mm were randomly assigned to receive implantation of a C-loop haptic toric IOL (AcrySof Toric IOL) (Group A) or a plate-haptic toric IOL (AT TORBI 709M IOL) (Group B). IOL rotation, residual astigmatism, visual acuity, and higher-order aberrations (HOAs) evaluated with OPD-Scan III aberrometer were compared at 3 months postoperatively. RESULTS: In total, 62 eyes of 62 patients were eligible for analysis: 31 in Group A and 31 in Group B. The mean rotation of toric IOLs was greater in Group A than that in Group B (8.00 ± 3.60 degrees vs 4.42 ± 3.24 degrees, respectively, P < .001), especially when IOLs were vertically placed. IOL rotation was positively correlated with AL in Group A, whereas no such correlations were found in Group B. Residual astigmatism in Group A was greater than that in Group B (-0.76 ± 0.30 diopter [D] vs -0.51 ± 0.29 D, respectively, P = .001). Fewer eyes achieved residual astigmatism of 0.50 D or less in Group A than in Group B (38.71% vs 64.52%). Group A had worse postoperative uncorrected visual acuity and higher total HOAs and coma for a 6.0 mm pupil than Group B, whereas postoperative corrected visual acuity was not different between the 2 groups. CONCLUSIONS: The plate-haptic toric IOL might be a better choice for myopic cataract eyes with corneal astigmatism because of reduced postoperative rotation.

Exosomes from adipose-derived stem cells attenuate UVB-induced apoptosis, ROS, and the Ca2+ level in HLEC cells.

Cartilage acid protein 1 (CRTAC1) encodes a protein containing the Ca2+binding domain, which can promote apoptosis of human lens epithelial cells (HLECs) induced by ultraviolet B radiation. Exosomes secreted from adipose-derived stem cells (ASC-exo) have been used to treat many diseases, but the effect of ASC-exo on cataracts has not been established. We hypothesized that ASC-exo has a therapeutic effect on cataracts by regulating CRTAC1. We established the UVB-induced injured HLECs model to test the interactions between CRTAC1 and miR-10a-5p, and the effect on the Ca2+ level and reactive oxygen species (ROS) generation in apoptotic HLECs. We found that UVB significantly increased the level of CRTAC1 expression and induced HLEC apoptosis, while ASC-exo inhibited the induction of UVB and exosome inhibitor reduced the inhibition of ASC-exo. The qRT-PCR results showed that miR-10a-5p had a low level of expression in cataract lesions, whereas CRTAC1 was highly expressed. There was a negative correlation between the expression of CRTAC1 and miR-10a-5p. ASC-exo reversed UVB-inhibited miR-10a-5p expression and miR-10a-5p negatively regulated CRTAC1. In vitro data showed that miR-10a-5p reversed UVB-induced ROS, apoptosis, and the Ca2+ level in HLECs. Overexpression of CRTAC1 reversed the induction of ASC-exo in UVB-injured HLECs, and low expression of CRTAC1 reversed the induction of miR-10a-5p inhibitor. By upregulating the level of miR-10a-5p expression and downregulating the level of CRTAC1 expression, exosomes from ASCs attenuated UVB-induced apoptosis, ROS generation, and the Ca2+ level in HLECs. Our research provides novel insight into the treatment methods and associated mechanisms underlying cataracts.

Chronic Periodontitis and Alzheimer Disease: A Putative Link of Serum Proteins Identification by 2D-DIGE Proteomics.

Increasing evidence indicates Chronic Periodontitis (CP) is a comorbidity of Alzheimer's disease (AD), which is the most common form of age-related dementia, and for the latter, effective diagnostic and treatment strategies are lacking. Although inflammation is present in both diseases, the exact mechanisms and cross-links between CP and AD are poorly understood; and a direct association between the two has not been reported. This study aimed to identify a direct serum proteins link between AD and CP. Two-dimensional differential in-gel electrophoresis was employed to analyze serum samples from 12 CP patients and 12 age-matched controls. Furthermore, to determine the molecular link between CP and AD, neuroblastoma SK-N-SH APPwt cells were treated with 1 µg/ml of lipopolysaccharide from Porphyromonas gingivalis (P.g-LPS). Ten differentially expressed proteins were identified in CP patients. Among them, nine proteins were up-regulated, and one protein was down-regulated. Of the 10 differentially expressed proteins, five proteins were reportedly involved in the pathology of AD: Cofilin-2, Cathepsin B, Clusterin, Triosephosphate isomerase, and inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4). Western blotting indicated significantly higher expression of Cofilin-2, Cathepsin B, and Clusterin and lower expression of ITI-H4 in the CP group than in the Control group. The serum concentration of Cathepsin B has a good correlation with MMSE scores. Moreover, the protein level of Cathepsin B (but not that of ADAM10 and BACE1) increased significantly along with a prominent increase in Aß1-40 and Aß1-42 in the cell lysates of P.g-LPS-treated SK-N-SH APPwt cells. Cathepsin B inhibition resulted in a sharp decrease in Aß1-40 and Aß1-42 in the cell lysates. Furthermore, TNF-α was one of the most important inflammatory cytokines for the P.g-LPS-induced Cathepsin B upregulation in SK-N-SH APPwt cells. These results show that CP and AD share an association, while Cathepsin B could be a key link between the two diseases. The discovery of the identical serum proteins provides a potential mechanism underlying the increased risk of AD in CP patients, which could be critical for elucidating the pathophysiology of AD.

Down-regulation of CRTAC1 attenuates UVB-induced pyroptosis in HLECs through inhibiting ROS production.

Pyroptosis has been found to be related to diverse ocular diseases, including cataract. Abnormal CRTAC1 expression has been reported to involve in cataract formation by affecting cell apoptosis. Whether CRTAC1 regulates pyroptosis in the formation progress of cataract is completely unknown. Here, we aimed to investigate the regulatory effects of CRTAC1 on pyroptosis and the potential mechanism in the UVB-induced cell damage model. The results showed that the levels of the established pyroptosis markers (NLRP3, active Caspase-1, pro Caspase-1, GSDMD-N, IL-1ß and IL-18) were significantly increased in cataract patients. The above pyroptosis markers could be obviously induced by UVB-irradiation in human lens epithelial cells (HLECs), while down-regulation of CRTAC1 significantly reversed the UVB-induced pyroptosis. Up-regulation of CRTAC1 promoted HLECs pyroptosis, while the ROS inhibitor N-acetyl-l-cysteine blocked the effects of CRTAC1 overexpression. In conclusion, our findings further suggested that the prominent role of CRTAC1 in cataract formation.

Decentration and tilt of plate-haptic multifocal intraocular lenses in myopic eyes.

BACKGROUND: To investigate the decentration and tilt of plate-haptic multifocal intraocular lenses (MfIOLs) in myopic eyes. METHODS: Myopic (axial length [AXL] > 24.5 mm) and non-myopic (21.0 mm < AXL ≤ 24.5 mm) cataract eyes were enrolled in this prospective study and randomly assigned to receive implantation of Zeiss AT LISA tri 839MP lenses (Group A) or Tecnis ZMB00 lenses (Group B). In total, 122 eyes of 122 patients were available for analysis. Decentration and tilt of MfIOLs, high-order aberrations (HOAs), and modulation transfer functions (MTFs) were evaluated using the OPD-Scan III aberrometer 3 months postoperatively. Subjective symptoms were assessed with a Quality of Vision questionnaire. RESULTS: Near and distance visual acuities, tilt and horizontal decentration did not differ between the two groups, postoperatively. However, myopic eyes of Group B showed greater vertical decentration than those of Group A (- 0.17 ± 0.14 mm vs. -0.03 ± 0.09 mm, respectively), particularly when the MfIOLs were placed horizontally or obliquely. Overall decentration of myopic eyes was greater in Group B than in Group A (0.41 ± 0.15 mm vs. 0.16 ± 0.10 mm, respectively). In Group B, AXL was negatively correlated with vertical decentration and positively correlated with overall decentration. No such correlations were found in Group A. Intraocular total HOAs, coma, trefoil and spherical aberrations were lower in Group A than in Group B for a 6.0 mm pupil among myopic eyes. Generally, Group A had better MTFs and fewer subjective symptoms than Group B among myopic eyes. CONCLUSIONS: Plate-haptic design of MfIOLs may be a suggested option for myopic cataract eyes due to the less inferior decentration and better visual quality postoperatively.

The Necessity for Second-eye Cataract Surgery in Bilateral Highly Myopic Patients with Good Visual Acuity in the Unoperated Fellow Eye.

PURPOSE: To evaluate the necessity for second-eye cataract surgery in bilateral highly myopic patients with good visual acuity in the unoperated fellow eye. MATERIALS AND METHODS: Seventy-five bilateral highly myopic patients who underwent uneventful sequential cataract surgery (the eye with worse visual acuity operated first) were included in this prospective study. The preoperative BCVA of the eye with better visual acuity in these patients was ≤ 0.3 (logMAR, or Snellen ≥ 20/40). Binocular single vision examinations were performed 1 month after the first-eye and second-eye surgery, respectively. The VF-14 questionnaire was completed before first-eye surgery, 1 month after the first-eye and 1 month after the second-eye surgery, respectively. RESULTS: The first eye's postoperative SE was -3.07 ± 1.10D and the second eye's preoperative SE was -12.91 ± 5.15D. Binocular single vision functional parameters improved significantly after the second-eye cataract surgery compared with that after the first-eye surgery (all P < .001). The binocular single vision function was negatively correlated with the SE difference between the two eyes after the first-eye surgery. No difference was found between the scores of VF-14 questionnaire preoperatively and after the first-eye surgery. VF-14 score only improved significantly after the second-eye surgery compared with that after the first-eye surgery (P < .001). CONCLUSION: In bilateral highly myopic cataract patients, binocular single vision function could improve significantly after the second-eye cataract surgery compared with after the first-eye surgery. Bilateral highly myopic patients may undergo second-eye cataract surgery earlier, even if cataract in that eye is not severe enough to affect the visual acuity.

NF-κB/Cartilage Acidic Protein 1 Promotes Ultraviolet B Irradiation-Induced Apoptosis of Human Lens Epithelial Cells.

The apoptosis of human lens epithelial cells (HLECs) is a characteristic change that occurs during the development of cataracts. Ultraviolet B (UVB) is known to induce the generation of reactive oxygen species (ROS) and apoptosis in HLECs, and thus cause cataracts. Previously, we reported the functions of cartilage acidic protein 1 (CRTAC1) in UVB-treated HLECs. However, the underlying mechanism was not known. In this study, we found that CRTAC1 expression and nuclear factor-kappa B (NF-κB) p65 nuclear translocation were elevated in capsule tissues of cataract patients in comparison with normal controls. The NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), alleviated UVB-induced apoptosis in HLECs; while activation of NF-κB suppressed the effects of the ROS inhibitor, N-acetyl-L-cysteine (NAC), on UVB-treated HLECs. The expression and promoter activity of CRTAC1 was inhibited by PDTC and NAC. Moreover, the suppressed effects of CRTAC1 knockdown on UVB-induced ROS generation, cell apoptosis, nuclear translocation of NF-κB p65, and p38 phosphorylation were attenuated by a p38 agonist. In contrast, the p38 inhibitor abolished the promotional effects of CRTAC1 overexpression on HLECs. Taken together, our results for the first time show that NF-κB is a potential transcription factor for CRTAC1. The regulatory network involving NF-κB, CRTAC1, and p38 may therefore play an important role in cataract formation.

Case Series: Slight Intraocular Lens Malpositioning as a Potential Cause of Vision Loss.

SIGNIFICANCE: The cases illustrate an insidious cause of decreased visual acuity after cataract surgery. PURPOSE: The purpose of this study was to identify cases of postoperative vision loss caused by slight intraocular lens (IOL) malpositioning after cataract surgery. CASE REPORTS: Three patients presented with visual acuity decreased after cataract surgery. Silt-lamp examination before mydriasis revealed no abnormalities in two of the patients; mild IOL inferonasal decentration was found by the trifocal IOL diffraction ring in the third patient. Manifest refraction of these patients showed remarkable astigmatism with low corneal astigmatism. After pupil dilation, slight IOL decentration and tilt were observed in all patients, which were further confirmed using the Scheimpflug imaging system. Wavefront aberrometry showed a high level of ocular higher-order aberrations, most of which were derived from intraocular aberrations. CONCLUSIONS: Inconspicuous IOL malpositioning is one of the reasons responsible for decreased vision acuity after cataract surgery, which may not be easily identified by slit-lamp examination. High astigmatism and ocular higher-order aberrations derived from malpositioned IOL can be important clues.

Intraocular lens power calculation in eyes with extreme myopia: Comparison of Barrett Universal II, Haigis, and Olsen formulas.

PURPOSE: To compare the accuracy of the Barrett Universal II, Haigis, and Olsen formulas in calculating intraocular lens (IOL) power in eyes with extreme myopia. SETTING: Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China. DESIGN: Prospective case series. METHODS: Eyes were divided into 3 axial length (AL) groups as follows: 26.0 to 28.0 mm (control), 28.0 to 30.0 mm (extreme myopia 1), and 30.0 mm or more (extreme myopia 2). The mean error (ME) 1 month postoperatively was adjusted to zero by optimizing the lens factor; then, the median absolute errors (MedAEs) were compared between formulas. Factors associated with postoperative refractive errors were analyzed. RESULTS: After optimization, the MEs of the Barrett Universal II, Haigis, and Olsen formulas were 0.04 diopter (D) ± 0.48 (SD), 0.04 ± 0.66 D, and 0.04 ± 0.52 D, respectively, and the MedAEs were 0.37 D, 0.46 D, and 0.39 D, respectively (P = .044; Haigis versus Barrett: P = .038). In the extreme myopia 1 group, all 3 formulas produced small MedAEs (P = .662). In the extreme myopia 2 group, the Haigis formula produced a significantly greater MedAE than the Barrett Universal II formula (P = .007; Haigis versus Olsen: P = .055). The accuracy of the Haigis formula in myopic eyes was affected by the AL and keratometry value, whereas the accuracy of the Barrett Universal II and Olsen formulas was affected by the AL only. CONCLUSIONS: In eyes with an AL of 28.0 to 30.0 mm, all 3 formulas were accurate. In eyes with AL of 30.0 mm or more, the Barrett Universal II formula was better than the Haigis formula, possibly because there were fewer influencing factors.

TRIM69 inhibits cataractogenesis by negatively regulating p53.

Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.

Evaluation of the antioxidant effects of different histone deacetylase inhibitors (HDACis) on human lens epithelial cells (HLECs) after UVB exposure.

BACKGROUND: To compare the protective effects of the histone deacetylase inhibitors (HDACis) ß-hydroxybutyrate (ßOHB), trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on human lens epithelial cells(HLECs) following ultraviolet-B (UVB) exposure. METHODS: HLECs were divided into subgroups: four HDACi groups, a control group, a UVB-treated group and a DMSO group (cells treated with DMSO and UVB irradiation). In the HDACi groups, HLECs were cultured with different concentrations of HDACis 12 h prior to UVB irradiation. The protective effects of the HDACis were evaluated by assessing apoptosis rates, cell activity and expression levels of genes associated with apotosis (caspase-3, Bcl-2, BAX, SOD1, FOXO3A and MT2). The levels of superoxide dismutase (SOD), reactive oxygen species (ROS), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were detected in order to evaluate oxidative stress. RESULTS: The results showed that SAHA (1 µmol/L, 2 µmol/L) and TSA (0.2 µmol/L) had mild protective effects on cell viability. ßOHB (4 mmol/L) and TSA (0.2 mol/L) demonstrated protective effects on BCL-2 expression. TSA (0.2 mol/L) showed protective effects on SOD1 expression. TSA (0.2 mol/L) and SAHA (1 µmol/L) suppressed BAX and caspase-3 expression. TSA (0.2 mol/L, 0.8 mol/L) and SAHA (1 µmol/L, 2 µmol/L) suppressed the expression of FOXO3A and MT2. SOD levels were increased after treatment with ßOHB (4 mmol/L), SAHA (8 µmol/L) and TSA (0.1 mol/L, 0.2 mol/L). T-AOC levels were increased in UVB-treated HLECs after treatment with SAHA (2 µmol/L). MDA levels decreased in UVB-treated HLECs following treatment with TSA (0.2 mol/L, 0.8 mol/L). ROS levels decreased in UVB-treated HLECs following treatment with ßOHB (4 mmol/L), SAHA (1 µmol/L, 2 µmol/L) and TSA (0.2 mol/L). Western blotting results demonstrated that SOD1 levels significantly increased in the ßOHB (4 mmol/L), SAHA (1 µmol/L, 2 µmol/L), TSA (0.1 mol/L, 0.2 mol/L) and VPA (5 mmol/L) groups. Only SAHA (1 µmol/L) had an anti-apoptotic effect on UVB-treated HLECs. CONCLUSIONS: Our findings indicate that low concentrations of HDACis (1 µmol/L of SAHA) mildly inhibit oxidative stress, thus protecting HLECs from oxidation. These results may suggest that there is a possibility to explore the clinical applications of HDACis for treatment and prevention of cataracts.

Dome-shaped macula: a potential protective factor for visual acuity after cataract surgery in patients with high myopia.

PURPOSE: To evaluate whether the presence of dome-shaped macula (DSM) is a protective factor for visual acuity after cataract surgery in patients with high myopia. METHODS: Included were 891 highly myopic cataract eyes (600 patients) that were examined by optical coherence tomography (OCT) through the central fovea and underwent cataract surgery in our hospital. DSM was defined as an inward bulge >50 µm in horizontal or vertical OCT sections. The incidences of various maculopathies were compared between eyes with and those without DSM. The influences of age, sex, eye laterality, axial length and DSM on postoperative visual acuity were evaluated by multivariate linear regression. RESULTS: Of the 891 eyes, 123 (13.8%) had DSM. There was a greater association of DSM with extrafoveal retinoschisis (RS) than with other vision-threatening complications such as foveal RS and choroidal neovascularisation. In addition to axial length and age, sex was associated with the presence of DSM (p=0.016). In bilateral high myopia, the incidence of DSM increased with the degree of anisometropia and was more common in the longer eye of patients with anisometropia. Younger age, male sex, shorter axial length and the presence of DSM were associated with better postoperative visual acuity in highly myopic cataract eyes (ß=0.124, p=0.002; ß=0.142, p<0.001; ß=0.275, p<0.001 and ß=-0.088, p=0.038, respectively). CONCLUSION: Associated with fewer visual threatening macular complications, presence of DSM may be a protective factor for visual function after cataract surgery in highly myopic eyes.

Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats.

BACKGROUND: To pursuit effective sustained release systems for insulin to treat diabetic retinopathy (DR), a novel insulin delivering system was developed via loading onto chitosan nanoparticles/poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel (ICNPH). METHODS AND MATERIALS: Examinations including electroretinography, HE staining, transmission electron microscopy, terminal deoxynucleotidyl transferased UTP nick-end labeling, immunofluorescence, Western blot, and real-time polymerase chain reaction were performed to evaluate the neuroprotective efficacy of ICNPH on DR by a single subconjunctival injection. RESULTS: Compared with the insulin, blank, and sham treatment groups, subconjunctival injection of ICNPH significantly reduced the decrease of scotopic B-wave amplitude, alleviated retinal micro- and ultrastructural changes, and reduced retinal cell apoptosis caused in DR rats. Meanwhile, a significant reduction of vascular endothelial growth factor and glial fibrillary acidic protein expression as well as a remarkable increase in Occludin expression was also found in retinas in ICNPH group compared with the sham treatment group. CONCLUSION: The results indicate that ICNPH has sufficient neuroprotective effect on retinas through subconjunctival injection in DR rats and facilitates controlled insulin delivery. It might be one of the therapeutic strategies for DR in the near future.

Metabolic characterization of human aqueous humor in the cataract progression after pars plana vitrectomy.

BACKGROUND: While pars plana vitrectomy (PPV) has become the third most commonly performed surgery in the world, it can also induce multiple post complications easily. Among them, cataract progression is the most frequent one that can lead to blindness eventually. METHODS: To understand the underlying mechanisms of post PPV cataract progression, we performed comprehensive metabolic characterization of aqueous humor (AH) samples from 20 cataract patients (10 post PPV complication and 10 none PPV cataract) by a non-targeted metabolomic analysis using gas chromatography combined with time-of-flight mass spectrometer (GC/TOF MS). RESULTS: A total of 263 metabolites were identified and eight of them are determined to be significantly different (VIP ≥ 1 and p ≤ 0.05) between post PPV group and none PPV control group. The significantly changed metabolites included glutaric acid and pelargonic acid that play key roles in the regulation of oxidative stress and inflammatory responses. Furthermore, we constructed a metabolic regulatory network in each group based on metabolite-metabolite correlations, which reveals key metabolic pathways and regulatory elements including amino acids and lipids metabolisms that are related to cataract progression. CONCLUSIONS: Altogether, this work discovered some potential metabolite biomarkers for post PPV cataract diagnostics, as well as casted some novel insights into the underlying mechanisms of cataract progression after PPV.

Potassium 2-(1-hydroxypentyl)-benzoate attenuates neuronal apoptosis in neuron-astrocyte co-culture system through neurotrophy and neuroinflammation pathway.

Potassium 2-(1-hydroxypentyl)-benzoate (d,l-PHPB), a new drug candidate for ischemic stroke at the phase II clinic trial, has been shown to protect neurons by inhibiting oxidative injury and reducing neuron apoptosis in previous studies. But the mechanisms of d,l-PHPB remain to be studied. In this study, a neuron-astrocytes co-culture system was used to elucidate the roles of astrocytes in neuroprotection of d,l-PHPB under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. Our data showed that d,l-PHPB reduced neuronal apoptosis in mono-culture system and this effect was enhanced in neuron-astrocyte co-culture system under the OGD/R condition. Meanwhile, d,l-PHPB obviously increased the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which were mainly secreted from astrocytes, in the co-culture system after OGD/R. The PI3K/AKT and ERK signaling pathways as well as the p-TRKA/B receptors were involved in the process. In addition, the levels of TNF-α and IL-1ß secreted from astrocytes after OGD/R were markedly reduced after d,l-PHPB treatment, which was mainly due to the suppression of phosphorylated p38. In conclusion, the present study demonstrates that the neuroprotective effects of d,l-PHPB were improved by astrocytes, mainly mediated by increasing the release of BDNF/NGF and attenuating inflammatory cytokines.