Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial.

OBJECTIVE: To investigate whether letrozole pre-treatment is non-inferior to mifepristone pre-treatment, followed by misoprostol, for complete evacuation in the medical treatment of first-trimester missed miscarriage. DESIGN: Prospective open-label non-inferiority randomised controlled trial. SETTING: A university-affiliated hospital. POPULATION: We recruited 294 women diagnosed with first-trimester missed miscarriage who opted for medical treatment. METHODS: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24-48 h later by 800 µg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once-a-day for 3 days, followed by 800 µg misoprostol vaginally on the third (i.e. last) day of letrozole administration. MAIN OUTCOME MEASURES: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post-treatment. Secondary outcomes included induction-to-expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. RESULTS: The complete evacuation rates were 97.8% (95% CI 95.1%-100%) and 97.2% (95% CI 94.4%-99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non-inferiority). The mean induction-to-tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post-treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. CONCLUSIONS: Letrozole is non-inferior to mifepristone as a pre-treatment, followed by misoprostol, for the medical treatment of first-trimester missed miscarriage.

Proteomics identifies hypothermia induced adiponectin protects corneal endothelial cells via AMPK mediated autophagy in phacoemulsification.

AIM: To explore the molecular mechanism underlying the protective effect of hypothermic perfusion on the corneal endothelium during phacoemulsification. METHODS: Phacoemulsification was performed on New Zealand white rabbits. Perfusate at different temperatures was used during the operation, and the aqueous humor was collected for proteomic sequencing after the operation. Corneal endothelial cell injury was simulated by a corneal endothelial cell oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. Flow cytometry and evaluation of fluorescent LC3B puncta were used to detect apoptosis and autophagy, and western blotting was used to detect protein expression. RESULTS: A total of 381 differentially expressed proteins were identified between the two groups. In vitro, 4 ℃ hypothermia significantly reduced apoptosis and promoted autophagy. Apoptosis increased after autophagy was inhibited by 3-Methyladenine (3-MA). Furthermore, adiponectin (ADIPOQ) knockdown inhibited phospho-AMPK and blocked the protective effect of hypothermia on corneal endothelial cells. CONCLUSIONS: We investigated the differential expression of proteins between the hypothermia group and normothermia group by proteomics. Moreover, hypothermia-induced ADIPOQ can reduce apoptosis by promoting AMPK-mediated autophagy.

Crosstalk between heat shock factor 1 and signal transducer and activator of transcription 3 mediated by interleukin-8 autocrine signaling maintains the cancer stem cell phenotype in liver cancer.

BACKGROUND AND AIM: Liver cancer stem cells (LCSCs) cause therapeutic refractoriness and relapse in hepatocellular carcinoma. Heat shock factor 1 (HSF1) plays versatile roles in multiple cancers. However, the role of HSF1 in LCSCs is not well understood. This study investigated the function and signal mechanisms of HSF1 in maintaining LCSC phenotypes. METHODS: We established two LCSC lines, HepG2-R and HuH-7-R. Constitutive activation of HSF1 was observed in these LCSCs. Specific short hairpin RNAs (shRNAs) and chemical inhibitors were used to identify the relationship between HSF1 expression and LCSCs phenotypes. RESULTS: We revealed a concomitant activation modality involving HSF1 and STAT3 in LCSCs and liver cancer tissues. We also found that liver cancer patients whose HSF1 and STAT3 mRNA expression levels were high presented with unfavorable clinicopathological characteristics. Moreover, the secretion of interleukin-8 (IL-8) was elevated in the LCSC medium and was directly regulated by HSF1 at the transcriptional level. In turn, IL-8 activated HSF1 and STAT3 signaling, and a neutralizing IL-8 antibody inhibited HSF1 and STAT3 activity, reduced cancer stem cell marker expression, and decreased LCSC microsphere formation. Simultaneous intervention with HSF1 and STAT3 led to synergistically suppressed stemness acquisition and growth suppression in the LCSCs in vivo and in vitro. CONCLUSIONS: Our study indicates that IL-8 mediates the crosstalk between the HSF1 and Stat3 signaling pathways in LCSCs and that the combined targeting of HSF1 and STAT3 is a promising treatment strategy for patients with advanced liver cancer.

Comprehensive evaluation of functional vision, quality of life, and cognitive ability in pediatric uveitis.

BACKGROUND: Pediatric uveitis may cause severe impairment of vision in children and affect their quality of life as well as cognitive ability. This study aims to evaluate the functional vision, visual-related and health-related quality of life, and cognitive ability in pediatric uveitis. METHODS: Children with uveitis aged 5-16 years old completed six validated instruments to assess functional visual ability with Cardiff Visual Ability Questionnaire for Children (CVAQC), vision-related quality of life with Impact of Vision Impairment for Children (IVI-C), health-related quality of life with Pediatric Quality of Life Inventory (PedsQL), cognitive ability with Chinese Wechsler Intelligence Scale for Children (C-WISC), and depression and anxiety evaluation with Hospital Anxiety and Depression Scale (HAD). RESULTS: The CVAQC, IVI-C, and PedsQL scores of pediatric uveitis were significantly lower than that of normal levels. Full-scale intelligence quotient (IQ) and performance IQ were significantly lower in pediatric uveitis patients with impaired vision in their best eye (visual acuity < 0.3) compared to those with a vision equal to or better than 0.3. Verbal IQ was significantly lower in male pediatric uveitis patients with impaired vision compared to those with a vision equal to or better than 0.3. Additionally, parents of pediatric uveitis patients with impaired vision generally had lower educational levels than parents of those with a vision equal to or better than 0.3. CONCLUSIONS: Impaired vision caused by pediatric uveitis has a significant impact on children's functional visual ability and quality of life. The development of cognitive function in pediatric uveitis is also significantly hindered.

Efficacy of cataract surgeries performed during blindness prevention programs in Chongqing, China: a multicenter prospective study.

OBJECTIVE: To determine the efficacy of cataract surgeries in blindness prevention programs in Chongqing. METHODS: During February-December 2019, we prospectively enrolled 487 patients (592 eyes) undergoing cataract surgery during blindness prevention programs in 6 Chongqing district/county hospitals (experimental group) and 481 patients (609 eyes) undergoing cataract surgery in the First Affiliated Hospital of Chongqing Medical University (controls). Uncorrected visual acuity (UCVA), refractive status, best corrected visual acuity (BCVA), slit lamp examination, and visual function/quality of life (VF-QOL) questionnaire scores were evaluated preoperatively, and at 1 and 6 months postoperatively. RESULTS: In the experimental group, UCVA, BCVA, and VF-QOL scores at 1 and 6 months were better than the preoperative values (P < 0.05), but lower than the control-group values (P < 0.05). Rates of good UCVA and BCVA outcomes (≤ 0.5 logMAR) in the experimental group were 76.2% and 87.6%, respectively, at 1 month and 68.9% and 83.1%, respectively, at 6 months. Most eyes in the experimental (82.1%) and control (89.5%) groups had refractive errors within ± 1 D at 1 month. At 6 months, posterior capsule opacification (PCO) was more common in the experimental group (20.9% vs. 15.0%, P < 0.05). At 6 months, the main causes of visual impairment (UCVA > 0.5 logMAR) in the experimental group were uncorrected refractive errors (33.0%), PCO (29.5%), and fundus diseases (33.9%). CONCLUSION: Cataract surgeries in blindness prevention programs in Chongqing significantly improved visual acuity, VF, and QOL, but underperformed compared to surgeries in the tertiary teaching hospital.

Comparisons of visual outcomes between bilateral implantation and mix-and-match implantation of three types intraocular lenses.

PURPOSE: To compare binocular static visual acuity (SVA), stereopsis, contrast sensitivity (CS) and dynamic visual acuity (DVA) of 5 combinations of bifocal intraocular lenses (IOLs), trifocal IOLs and extended-depth-of-focus (EDOF) IOLs in age-related cataract patients. METHODS: Two hundred and ninety-two eyes of 146 patients who underwent cataract surgery in the ophthalmology department of the First Affiliated Hospital of Chongqing Medical University were involved. Subgroups included group MM (33patients, bilaterally bifocal IOL, ZMB00), group TT (31patients, bilaterally trifocal IOL, AT LISA tri839MP), group XX (34patients, bilaterally EDOF IOL, ZXR00), group MX (25patients, bifocal IOL, ZMB00 + EDOF IOL, ZXR00) and group TX (23patients, trifocal IOL, AT LISA tri839MP + EDOF IOL, ZXR00). The uncorrected SVAs (UDVA, UIVA and UNVA), uncorrected DVAs (UDDVA, UIDVA and UNDVA), near and distance stereopsis, and CS were assessed 3 months postoperatively. RESULTS: Subgroups of TT, XX, MX and TX showed better UIVA than MM (bP = 0.039, 0.021, 0.035 and 0.037, respectively). MX showed better UNVA than MM and TX (bP = 0.031 and 0.013, respectively). MX group had the optimal outcomes of both near and distance stereopsis. In the UDDVA, XX group and MX group showed better outcomes than TX group at 24 fps (frames per second) (bP = 0.019 and 0.023, respectively). XX group and MX group showed optimal outcomes at all speeds of UIDVA (P = 0.001, 0.005, 0.003 and 0.005, respectively). As the speed increased, the XX group and the MX group showed better UNDVA than the MM group and the TT group (P = 0.019, 0.002 and 0.003, respectively). CONCLUSIONS: Mix-and-match implantation of bifocal IOLs and EDOF IOLs provides excellent and stable binocular visual outcomes including SVA, stereopsis and DVA in distant and near distances.

Ocular microbial diversity, community structure, and function at high altitude.

PURPOSE: To investigate the composition and function of ocular surface microbiome in healthy people from different altitudes. METHODS: Thirty-two healthy people living in a high altitude region and 30 sex- and age-matched individuals living in a low altitude region were enrolled. Samples were collected from the lower conjunctival sac of one randomly chosen eye for each participant. 16S rRNA sequencing was conducted to study the bacterial community composition and predict gene function using PICRUSt software. RESULTS: Microbial diversity and richness was significantly decreased in samples from highlanders as calculated by Abundance-based Coverage Estimator (ACE) index, Chao1 index, and observed-species index (all p < 0.01). Principle coordinate analysis (PCoA) suggested significantly distinct clustering of the conjunctival sac bacterial communities between two groups (p = 0.03), especially the dominant genera. The relative abundances of Corynebacterium, Staphylococcus, and Anaerococcus were significantly enriched in highlanders, while those of Pseudomonas and Massilia were significantly decreased as compared with lowlanders (p < 0.01). In the functional annotation analysis, we found that 74 gene pathways, mainly in metabolism, differed in abundance. Pathways related to immune system diseases and infectious diseases were also enriched in highlanders. CONCLUSION: The composition and function of ocular surface microbiome in highlanders were distinct from those of lowlanders and our study may provide a reference catalog of the healthy conjunctival microbiome in highlanders.

Increase in electroretinogram rod-driven peak frequency of oscillatory potentials and dark-adapted responses in a cohort of myopia patients.

PURPOSE: To study whether rod- and cone-driven electroretinogram (ERG) responses are altered in myopia patients. METHODS: Dark- and light-adapted ERGs were recorded from 57 myopic eyes of 32 patients aged 22-30 and 19 emmetropic eyes of 10 age-matched normal subjects. The myopic eyes were divided into 3 groups according to spherical equivalent (SE) of manifest refraction: 18 low myopia eyes (≤ - 3.00 diopter (D), 23 moderate myopia eyes (- 3.25 to - 6.00 D), and 16 high myopia eyes (> - 6.25 D). The amplitudes of the dark- and light-adapted ERG a- and b-waves, as well as the frequency spectra of the cone-driven and rod-driven oscillatory potentials (OPs), were analyzed by fast Fourier transform. The peak frequency, implicit time, and total power of the OPs were determined. The axial length was measured with an IOL Master. The ERG parameters including those of the cone- and rod-driven OPs were compared among three groups. RESULTS: The amplitudes of the a-wave and b-wave of the dark-adapted ERGs were increased with refractive power (P < 0.05). Interestingly, the average peak frequency of the rod-driven OPs showed a significant positive correlation with refractive power (P < 0.001): 123.41 ± 9.13 Hz in emmetropic controls, 129.12 ± 10.28 Hz in low myopia, 133.90 ± 9.13 Hz in moderate myopia, and 139.51 ± 5.78 Hz in high myopia. However, the parameters of the light-adapted ERGs and the cone-driven OPs in myopic eyes were within normal ranges. CONCLUSION: We found significant positive correlation between the peak frequency of rod-driven OPs, as well as the amplitudes of rod-driven ERG a- and b-waves, and the refractive power. The results suggest that the rod system function was changing during the progress of myopia, while the cone system function appeared unaffected. The peak frequency of OPs appeared as a novel ERG parameter for myopia, a common ocular condition.

Crossed versus conventional pseudophakic monovision for high myopic eyes: a prospective, randomized pilot study.

BACKGROUND: Aiming at spectacle independence, conventional pseudophakic monovision has been widely used in myopia patients with bilateral monofocal intraocular lens implantation. However, the crossed monovision, which is to correct the dominant eye for near vision and the non-dominant eye for distant vision, has been mentioned preferable for high myopic cataract patients by some studies. We have conducted this study to compare clinical results to assess the feasibility of conventional and crossed monovision for high myopic pseudophakic patients by comparing patient satisfaction, visual function and spectacle independence. METHOD: Forty-sixth high myopia patients were divided into two groups: 22 in crossed monovision group with patients whose refraction targeted to - 2.00 diopters (D) in the dominant eye and - 0.50D in the non-dominant eye; 24 in conventional monovision group with patients whose refraction targeted to - 0.50D in the dominant eye and - 2.00D in the non-dominant eye. Binocular uncorrected distance visual acuity (BUDVA), binocular uncorrected near visual acuity (BUNVA), binocular corrected distant visual acuity (BCDVA), binocular corrected near visual acuity (BCNVA), contrast visual acuity and stereoacuity were examined at postoperative 2 weeks, 1 month and 3 months. Questionnaires were completed by patients 3 months after binocular surgery to evaluate patients' satisfaction and spectacle independence. RESULTS: The conventional monovision and the crossed monovision group showed no significant differences of mean BUDVA, BUNVA, BCDVA, BCNVA 2 weeks, 1 month or 3 months postoperatively (P > 0.05). There was no difference in the bilateral contrast sensitivity or stereoscopic function between the convention conventional and crossed monovision groups (P > 0.05). Patient satisfaction with near and distant vision, as well as spectacle dependence did not differ significantly between the two groups (P > 0.05). CONCLUSION: Crossed pseudophakic monovision exhibited similar visual function when compared with conventional monovision technique, which indicates that it is an effective option to improve the visual functionality and quality of life for high myopic patients who considering bilateral cataract surgery. TRIAL REGISTRATION: The Institutional Review Board and Ethics committee of the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. The trial registration was submitted in September 2018 and passed on March 18, 2020, and the registration number is: ChiCTR2000030935 .

Effect of hypothermic perfusion on phacoemulsification in cataract patients complicated with uveitis: a randomised trial.

BACKGROUND: To evaluate the effectiveness and safety of hypothermic perfusion in the phacoemulsification of cataract caused by uveitis. METHODS: This was a prospective, single-masked, randomised, controlled clinical trial. One hundred and six patients with uveitis-associated cataract underwent phacoemulsification with perfusion fluid temperature at 4 °C (treatment group) or 24 °C (control group). Anterior chamber inflammation grade, corneal endothelial cell count, corneal thickness, macular fovea thickness, and intraocular pressure (IOP) were observed on the 1st day and 7th day after operation. RESULTS: The aqueous flare score was 0.83 ± 0.76 in the 4 °C group, which was lower than that in the 24 °C group (1.51 ± 1.02, p = 0.006) on the first day after operation. The aqueous cells score was lower in the 4 °C group (0.17 ± 0.38) than that in the 24 °C group (0.62 ± 0.94, p = 0.025). The mean corneal thickness of incision in the 4 °C group (907.66 ± 85.37 µm) was thinner than that in the 24 °C group (963.75 ± 103.81 µm, p = 0.005). Corneal endothelial cells density, macular fovea thickness, or percentage of transiently increased IOP showed no difference between the two groups (p > 0.05). There was no significant difference in all the main outcome parameters between the two groups on the 7th day after operation (p > 0.05). CONCLUSIONS: Hypothermic perfusion in the phacoemulsification of uveitis-associated cataract is safe, and it can effectively inhibit anterior chamber inflammation and reduce the incisional corneal edema in the early postoperative stage. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry. (http://www.chictr.org.cn/, Registration Number: ChiCTR1800016145).

Creeping attachment: A literature review.

OBJECTIVE: Mucogingival surgery has been widely applied in clinics. An interesting phenomenon after mucogingival surgery is the coronal migration of gingival margin, which is described as "creeping attachment." The goal of this review is to summarize the characteristics, significance, mechanism, and manifestation of the creeping attachment after mucogingival surgery and to describe the factors associated with its occurrence. OVERVIEW: A total of 82 relevant articles were included in the literature review. The characteristics and significance of the creeping attachment after mucogingival surgery were analyzed. The mechanism of the creeping attachment was explored. Different manifestations of and factors associated with creeping attachment were summarized. CONCLUSIONS: Creeping attachment may occur to obtain additional root coverage after the healing of various mucogingival surgeries. However, this coverage is not always complete nor entirely predictable. CLINICAL SIGNIFICANCE: Creeping attachment plays an important role in the prognosis of mucogingival surgeries. This review will help clinicians get a thorough recognition and understanding of this phenomenon.

Comparing safety and efficiency of two closed-chamber techniques for iridodialysis repair - a retrospective clinical study.

BACKGROUND: This study aims to compare the safety and effectiveness of two closed-chamber techniques for repairing iridodialysis. METHODS: Seventy five patients with iridodialysis undergoing surgery from February 2008 to October 2017 were included in this study. Patients were divided into two Groups, Group A (32 eyes) and Group B (35 eyes), with Group A using a 26-gauge hypodermic needle guided 10-0 nylon suture, and Group B using a double-armed polypropylene suture. Before operation and 1, 3, and 6 months after the operation, pupil shape, best corrected visual acuity (BCVA), intraocular pressure (IOP), the rate of endothelial cell loss, and intra- and postoperative complications were compared between two Groups during the follow-up period. RESULTS: Iridodialysis was repaired with pupil shape restored in all cases. IOP was normalized in all eyes except 2 eyes (6.3%) in Group A and 3 eyes (8.6%) in Group B. Postoperative rate of endothelial cell loss was not significantly different between two Groups (P > 0.05). The percentage of complicated cataract was not significantly different in Group A (2 eyes, 6.3%) compared to Group B (2 eyes, 5.7%) (χ2 = 0.009, P = 0.658). CONCLUSIONS: Both techniques for repairing iridodialysis not only were safe but also effective in improving visual function and cosmetic recovery. However, double-armed polypropylene suture might be less invasive than 26-gauge hypodermic needle guided suture.

Effect of 7-methylxanthine on human retinal pigment epithelium cells cultured in vitro.

Purpose: To evaluate the effects of 7-methylxanthine (7-MX) on the growth of human retinal pigment epithelium (RPE) cells and to observe the changes in the expression of adenosine receptors (ADORs) in RPE cells upon 7-MX treatment. Methods: Human RPE cells (monolayer at about 80% confluence) were cultured in vitro in the presence or absence of 7-MX. Cell proliferation was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The cell cycle distribution and apoptosis level were analyzed with flow cytometry. Quantitative PCR and immunofluorescence assay were used to examine the mRNA and protein expression of ADORs. Results: 7-MX at low concentrations had no effect on the proliferation of RPE cells, whereas 100 µmol/l 7-MX slightly decreased cell proliferation at 48 h but without a statistically significant difference. The 7-MX treatment was performed at the low concentration of 10 µmol/l in the following experiments. The proportion of RPE cells in the G1 stage was slightly increased at 24 h (p=0.035) but decreased at 48 h (p=0.0045) upon 7-MX treatment; and the proportion was restored to normal at 72 h. No statistically significant change in apoptosis levels was found in RPE cells cultured with 7-MX. The expression of ADORA1, ADORA2A, and ADORA2B in RPE cells was inhibited by 7-MX treatment at 48 h, while the expression levels appeared to rebound at 72 h. Conclusions: 7-MX has little effect on the proliferation or apoptosis level of human RPE cells; however, in short-term treatment, 7-MX disturbs the proportion of cells in the G1 stage and inhibits the expression of ADORA1, ADORA2A, and ADORA2B.

Genipin ameliorates diabetic retinopathy via the HIF-1α and AGEs-RAGE pathways.

BACKGROUND: Traditional Chinese medicine (TCM) is useful in disease treatment and prevention. Genipin is an active TCM compound used to treat diabetic retinopathy (DR). In this study, a network pharmacology (NP)-based approach was employed to investigate the therapeutic mechanisms underlying genipin administration in DR. METHODS: The potential targets of DR were identified using the gene expression omnibus (GEO) database. TCM database screening and NP were used to predict the potential active targets and pathways of genipin in DR. Cell viability was tested in vitro to determine the effects of different doses of glucose and genipin on Human Retinal Microvascular Endothelial Cells (hRMECs). CCK-8, CCK-F, colony formation, CellTiter-Lum, Annexin V-FITC, wound healing, Transwell, tube-forming, reactive oxygen species (ROS), and other assay kits were used to detect the effects of genipin on hRMECs during high levels of glucose. In vivo, a streptozotocin (STZ)-mouse intraocular genipin injection (IOI.) model was used to explore the effects of genipin on diabetes-induced retinal dysfunction. Western blotting was performed to identify the cytokines involved in proliferation, apoptosis, angiogenesis, ROS, and inflammation. The protein expression of the AKT/ PI3K/ HIF-1α and AGEs/ RAGE pathways was also examined. RESULTS: Approximately 14 types of TCM, and nearly 300 active ingredients, including genipin, were identified. The NP approach successfully identified the HIF-1α and AGEs-RAGE pathways, with the EGR1 and UCP2 genes, as key targets of genipin in DR. In the in vitro and in vivo models, we discovered that high glucose increased cell proliferation, apoptosis, angiogenesis, ROS, and inflammation. However, genipin application regulated cell proliferation and apoptosis, inhibited angiogenesis, and reduced ROS and inflammation in the HRMECs exposed to high glucose. Furthermore, the retinal thickness in the genipin-treated group was lower than that in the untreated group. AKT/ PI3K/ HIF-1α and AGEs/ RAGE signaling was increased by high glucose levels; however, genipin treatment decreased AKT/ PI3K and AGEs/ RAGE pathway expressions. Genipin also increased HIF-1α phosphorylation, oxidative phosphorylation of ATP synthesis, lipid peroxidation, and the upregulation of oxidoreductase. Genipin was found to protect HG-induced hRMECs and the retina of STZ-mice, based on; 1 the inhibition of UCP2 and Glut1 decreased intracellular glucose, and glycosylation; 2 the increased presence of HIF-1α, which increased oxidative phosphorylation and decreased substrate phosphorylation; 3 the increase in oxidative phosphorylation from ATP synthesis increased lipid peroxidation and oxidoreductase activity, and; 4 the parallel effect of phosphorylation and glycosylation on vascular endothelial growth factor (VEGF), MMP9, and Scg3. CONCLUSION: Based on NP, we demonstrated the potential targets and pathways of genipin in the treatment of DR and confirmed its effective molecular mechanism in vitro and in vivo. Genipin protects cells and tissues from high glucose levels by regulating phosphorylation and glycosylation. The activation of the HIF-1α pathway can also be used to treat DR. Our study provides new insights into the key genes and pathways associated with the prognosis and pathogenesis of DR.

Myopia prevalence and ocular biometry in children and adolescents at different altitudes: a cross-sectional study in Chongqing and Tibet, China.

OBJECTIVE: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China. DESIGN: Cross-sectional study. SETTING: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet. PARTICIPANTS: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study. METHODS: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)). RESULTS: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude. CONCLUSIONS: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening.

Palladium nanocrystals regulates scleral extracellular matrix remodeling in myopic progression by modulating the hypoxia signaling pathway Nrf-2/Ho-1.

Myopia represents a widespread global public health concern influenced by a combination of environmental and genetic factors. The prevailing theory explaining myopia development revolves around scleral extracellular matrix (ECM) remodeling, characterized by diminished Type I collagen (Col-1) synthesis and increased degradation, resulting in scleral thinning and eye axis elongation. Existing studies underscore the pivotal role of scleral hypoxia in myopic scleral remodeling. This study investigates the peroxidase-like activity and catalytic performance of octahedral Palladium (Pd) nanocrystals, recognized as nanozymes with antioxidative properties. We explore their potential in reducing oxidative stress and alleviating hypoxia in human scleral fibroblasts (HSF) and examine the associated molecular mechanisms. Our results demonstrate the significant peroxidase-like activity of Pd nanocrystals. Furthermore, we observe a substantial reduction in oxidative stress in HSF under hypoxia, mitigating cellular damage. These effects are linked to alterations in Nrf-2/Ho-1 expression, a pathway associated with hypoxic stress. Importantly, our findings indicate that Pd nanocrystals contribute to attenuated scleral matrix remodeling in myopic guinea pigs, effectively slowing myopia progression. This supports the hypothesis that Pd nanocrystals regulate myopia development by controlling oxidative stress associated with hypoxia. Based on these results, we propose that Pd nanocrystals represent a novel and potential treatment avenue for myopia through the modulation of scleral matrix remodeling. This study introduces innovative ideas and directions for the treatment and prevention of myopia.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation.

BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization.

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin ß1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

Functional and morphological evaluation of the meibomian glands and ocular surface assessment at high altitude.

Purpose: To compare the function and morphology of the meibomian glands and the ocular surface of individuals from highland and lowland. Methods: This was a randomized controlled trial. The study was performed with 104 individuals (51 individuals from the highland and 53 individuals from the lowland). Detailed eye examinations comprising tear meniscus height, lipid layer grading, non-invasive Keratograph tear breakup time (NIKBUT), and scoring of the meibomian glands from the upper and lower eyelids of the individuals were performed by Keratograph 5M (OCULUS, Wetzlar, Germany). Symptoms related to dry eye disease were assessed using the Ocular Surface Disease Index (OSDI). Results: In the highland group, tear meniscus height was lower (P = 0.024), lipid layer grade, as well as all the meiboscores were higher (P < 0.05) than that in the lowland group. The OSDI (P = 0.018) and the percentage of dry eye disease were also higher as compared to that of the lowland group (P = 0.032). The first NIKBUT and average NIKBUT did not differ significantly between groups. The frequency of plugged meibomian gland orifices was greater in the lowland group compared to the highland group (P = 0.036). Conclusion: It was observed that dry eye disease was more common in the highland group. The morphological changes of meibomian gland dropout were significant in highlanders as demonstrated objectively with Keratograph 5M. Our study may raise a concern for environmental influences on ocular surface changes.