Current Eye Research最新文献

Purpose: Diabetic retinopathy (DR) is a major cause of irreversible blindness in the working-age population. Neovascularization is an important hallmark of advanced DR. There is evidence that Yes-associated protein (YAP)/transcriptional co-activator with a PDZ binding domain (TAZ) plays an important role in angiogenesis and that its activity is regulated by vascular endothelial growth factor (VEGF). Therefore, the aim of this study was to investigate the effect of YAP/TAZ-VEGF crosstalk on the angiogenic capacity of human retinal microvascular endothelial cells (hRECs) in a high-glucose environment.

Methods: The expression of YAP and TAZ of hRECs under normal conditions, hypertonic conditions and high glucose were observed. YAP overexpression (OE-YAP), YAP silencing (sh-YAP), VEGF overexpression (OE-VEGF) and VEGF silencing (sh-VEGF) plasmids were constructed. Cell counting kit-8 assay was performed to detect cells proliferation ability, transwell assay to detect cells migration ability, and tube formation assay to detect tube formation ability. The protein expression of YAP, TAZ, VEGF, matrix metalloproteinase (MMP)-8, MMP-13, vessel endothelium (VE)-cadherin and alpha smooth muscle actin (α-SMA) was measured by western blot.

Results: The proliferation of hRECs was significantly higher in the high glucose group compared with the normal group, as well as the protein expression of YAP and TAZ (p < 0.01). YAP and VEGF promoted the proliferation, migration and tube formation of hRECs in the high glucose environment (p < 0.01), and increased the expression of TAZ, VEGF, MMP-8, MMP-13 and α-SMA while reducing the expression of VE-cadherin (p < 0.01). Knockdown of YAP effectively reversed the above promoting effects of OE-VEGF (p < 0.01) and overexpression of YAP significantly reversed the inhibition effects of sh-VEGF on above cell function (p < 0.01).

Conclusion: In a high-glucose environment, YAP/TAZ can significantly promote the proliferation, migration and tube formation ability of hRECs, and the mechanism may be related to the regulation of VEGF expression.

Background: Dysregulated circular RNAs (circRNAs) is involved in the pathogenesis of age-related cataract (ARC). Here, this study aimed to explore the function and mechanism of circMAP3K4 in ARC.

Methods: Human lens epithelial cells were exposed to hydrogen peroxide (H2O2) for functional experiments. qRT-PCR and western blotting analyses were used for the expression detection of genes and proteins. Cell proliferation was tested using cell counting kit-8 and EdU. Flow cytometry was applied to analyze cell apoptosis and cell cycle. The oxidative stress was evaluated by detecting the production of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). The target relationship between miR-630 and circMAP3K4 or Excision repair cross-complementing group 6 (ERCC6) was analyzed by dual-luciferase reporter assay and RIP assay.

Results: CircMAP3K4 was lowly expressed in ARC patients and H2O2-induced HLECs. Functionally, forced expression of circMAP3K4 protected HLECs against H2O2-evoked proliferation inhibition, cell cycle arrest and the promotion of cell apoptosis and oxidative stress. Mechanistically, circMAP3K4 acted as a sponge for miR-630 to regulate the expression of its target ERCC6. MiR-630 was highly expressed while ERCC6 was lowly expressed in ARC patients and H2O2-induced HLECs. Up-regulation of miR-630 could reverse the protective effects of circMAP3K4 on HLECs under H2O2 treatment. In addition, inhibition of miR-630 suppressed H2O2-induced HLEC injury, which was abolished by ERCC6 silencing.

Conclusion: Forced expression of circMAP3K4 protected HLECs against H2O2-evoked apoptotic and oxidative injury via miR-630/ERCC6 axis, suggesting that circMAP3K4 may function as a potential therapeutic target for ARC.

Purpose: Drugs administered in the ocular region need to overcome ocular barriers without permanently damaging the ocular tissues. Moreover, ocular disorders of the posterior segment are more difficult to treat due to invasive procedures required to reach the posterior segment. Hence, to treat posterior disorders of the eye an attempt was made to develop nanofiber (NF) scaffolds for effective management of chronic posterior uveitis. Nanofibers (NFs) were formulated using the electrospinning technique.

Methods: NF scaffolds were formulated using the electrospinning technique. The effect of different concentrations of chitosan on NF production was studied by considering different ratios of chitosan (CS) and polyvinyl alcohol (PVA). Physicochemical characterization of NFs was performed to evaluate developed NFs.

Results: The optimized NF scaffold had a diameter of 129 ± 3 nm. NF scaffolds were found to have a tensile strength of 0.2882 ± 0.078 N/m², thickness of 0.16 ± 0.05 mm, and drug entrapment of 95 ± 2.0%. The bioadhesive strength of the NF was found to be 257.3 ± 0.04 g/cm² indicating high bioadhesion of NFs to the ocular tissues. The in-vitro, ex-vivo corneal and ex-vivo scleral drug release after 12 h was found to be 78.4 ± 1.0%, 65.33 ± 0.2% and 78.41 ± 1.0%, respectively. Ex-vivo whole eye model experiment indicated a concentration of about 40 ± 1.75% of drug permeated from corneal layer to the vitreous humor after 12 h. The Hen's egg test-chorioallantoic membrane study (HET-CAM) study and in-vitro cytotoxicity study on Statens Seruminstitut Rabbit Cornea (SIRC) cell lines indicated that the developed drug-loaded NF scaffolds were found to be non-toxic as compared to pure drug, thus suggesting cytocompatibility.

Conclusion: Results of HET-CAM, sterility and ex-vivo studies indicate that the developed formulation is non-toxic, sterile, and effective for the ocular delivery of fluocinolone acetonide to the posterior segment of eye.

Purpose: Diagnosis of Uveitic Macular Edema (UME) using Spectral Domain OCT (SD-OCT) is a promising method for early detection and monitoring of sight-threatening visual impairment. Viewing multiple B-scans and identifying biomarkers is challenging and time-consuming for clinical practitioners. To overcome these challenges, this paper proposes an image classification hybrid framework for predicting the presence of biomarkers such as intraretinal cysts (IRC), hyperreflective foci (HRF), hard exudates (HE) and neurosensory detachment (NSD) in OCT B-scans along with their severity.

Methods: A dataset of 10880 B-scans from 85 Uveitic patients is collected and graded by two board-certified ophthalmologists for the presence of biomarkers. A novel image classification framework, Dilated Depthwise Separable Convolution ResNet (DDSC-RN) with SVM classifier, is developed to achieve network compression with a larger receptive field that captures both low and high-level features of the biomarkers without loss of classification accuracy. The severity level of each biomarker is predicted from the feature map, extracted by the proposed DDSC-RN network.

Results: The proposed hybrid model is evaluated using ground truth labels from the hospital. The deep learning model initially, identified the presence of biomarkers in B-scans. It achieved an overall accuracy of 98.64%, which is comparable to the performance of other state-of-the-art models, such as DRN-C-42 and ResNet-34. The SVM classifier then predicted the severity of each biomarker, achieving an overall accuracy of 89.3%.

Conclusions: A new hybrid model accurately identifies four retinal biomarkers on a tissue map and predicts their severity. The model outperforms other methods for identifying multiple biomarkers in complex OCT B-scans. This helps clinicians to screen multiple B-scans of UME more effectively, leading to better treatment outcomes.

Purpose: Mutations in transforming growth factor beta-induced (TGFBI) protein are associated with a group of corneal dystrophies (CDs), classified as TGFBI-associated CDs, characterized by deposits in the cornea. Mouse models were not proper in several aspects for modelling human disease. The goal of this study was to generate zebrafish mutants to investigate the corneal phenotype and to decide whether zebrafish could be a potential model for TGFBI-associated CDs.

Methods: The conserved arginine residue, codon 117, in zebrafish tgfbi gene was targeted with Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 method. Cas9 VQR variant was used with two target-specific sgRNAs to generate mutations. The presence of mutations was evaluated by T7 Endonuclease Enzyme (T7EI) assay and the type of the mutations were evaluated by Sanger sequencing. The mutant zebrafish at 3 months and 1 year of age were investigated under the microscope for corneal opacity and eye sections were evaluated histopathologically with hematoxylin-eosin, masson-trichrome and congo red stains for corneal deposits.

Results: We achieved indel variation at the target sequence that resulted in p.Ser115_Arg117delinsLeu (c. 347_353delinsT) by nonhomology mediated repair in F1. This zebrafish mutation had the potential to mimic two disease-causing mutations reported in human cases previously: R124L and R124L + del125-126. Mutant zebrafish did not show any corneal opacity or corneal deposits at 3 months and 1 year of age.

Conclusion: This study generated the first zebrafish model mimicking the R124 hot spot mutation in TGFBI-associated CDs. However, evaluations even at 1 year of age did not reveal any deposits in the cornea histopathologically. This study increased the cautions for modelling TGFBI-associated CDs in zebrafish in addition to differences in the corneal structure between zebrafish and humans.

Purpose: To examine the long-term effect of combined blepharoplasty and Müller muscle-conjunctival resection (MMCR) compared to an upper blepharoplasty procedure on dry eye syndrome.

Methods: This is a Prospective comparative case series. Two groups of patients participated in this study: the blepharoplasty group included adult patients that underwent blepharoplasty at least 3 years earlier and the ptosis group consisting of adult patients that underwent MMCR with blepharoplasty at least 3 years earlier. The parameters that were compared for all patients before the procedure, on postoperative day 90, and at the long-term follow-up were: Schirmer-test 2, tear break-up time (TBUT), fluorescein staining, and lissamine green (LG) staining.

Results: The participants included 25 post-MMCR patients with a mean follow-up of 4.94 ± 0.64 years and 15 post-blepharoplasty patients with a mean follow-up of 4.22 ± 0.32 years. There was a significant increase in the postoperative LG and fluorescein staining scores compared to the preoperative scores in the ptosis group (p < .01 and p < .01, respectively) as well as a decrease in postoperative TBUT compared to the preoperative values (p = .044). Those parameters were not significant in the blepharoplasty group.

Conclusions: Patients who underwent MMCR, but not those following upper blepharoplasty, showed signs of dry eye compared to the preoperative status after long-term follow-up. Dry eye signs should be examined before MMCR surgery, and patients should be aware of the high risk of developing dry eye and the need for long-term treatment. Surgeons should carefully consider performing MMCR for patients with severe dry eye.

Purpose: Metformin, a biguanide antihyperglycemic drug, can exert various beneficial effects in addition to its glucose-lowering effect. The effects of metformin are mainly mediated by AMP-activated protein kinase (AMPK)-dependent pathway. AMPK activation interferes with the action of the mammalian target of rapamycin complex 1 (mTORC1), and blockade of mTORC1 pathway suppresses pathological retinal angiogenesis. Therefore, in this study, we examined the effects of metformin on pathological angiogenesis and mTORC1 activity in the retinas of mice with oxygen-induced retinopathy (OIR).

Methods: OIR was induced by exposing the mice to 80% oxygen from postnatal day (P) 7 to P10. The OIR mice were treated with metformin, rapamycin (an inhibitor of mTORC1), or the vehicle from P10 to P12 or P14. The formation of neovascular tufts, revascularization in the central avascular areas, expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 2, and phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTORC1 activity, were evaluated at P10, P13, or P15.

Results: Neovascular tufts and vascular growth in the central avascular areas were observed in the retinas of P15 OIR mice. The formation of neovascular tufts, but not the revascularization in the central avascular areas, was attenuated by metformin administration from P10 to P14. Metformin had no significant inhibitory effect on the expression of VEGF and VEGFR2, but it reduced the pS6 immunoreactivity in vascular cells at the sites of angiogenesis. Rapamycin completely blocked the phosphorylation of ribosomal protein S6 and markedly reduced the formation of neovascular tufts.

Conclusions: These results suggest that metformin partially suppresses the formation of neovascular tufts on the retinal surface by blocking the mTORC1 signaling pathway. Metformin may exert beneficial effects against the progression of ocular diseases in which abnormal angiogenesis is associated with the pathogenesis.

Purpose: To evaluate prediction accuracy of pre- and post-DMEK keratometry (K) and total keratometry (TK) values for IOL power calculations in Fuchs endothelial corneal dystrophy (FECD) eyes undergoing DMEK with cataract surgery (triple DMEK).

Methods: Retrospective cross-sectional multicenter study of 55 FECD eyes (44 patients) that underwent triple DMEK between 2019 and 2022 between two centers in USA and Europe. Swept-source optical coherence tomography biometry (IOLMaster 700) was used for pre- and post-DMEK measurements. K and TK values were used for power calculations with ten formulae (Barrett Universal II (BUII), Castrop, Cooke K6, EVO 2.0, Haigis, Hoffer Q, Hoffer QST, Holladay I, Kane, and SRK/T). Mean error, mean absolute error (MAE), standard deviation, and percentage of eyes within ±0.50/±1.00 diopters (D) were calculated. Studied formulae were additionally adjusted using a method published previously (IOLup1D Method), which increases the IOL power by 1D. While both eyes from the same patient were considered for descriptive statistics, we restricted to one eye per individual (44 eyes for statistical comparisons.

Results: MAEs for all formulae were lower for post-DMEK K and TK than pre-DMEK K and TK by an average of 0.24 and 0.47 D, respectively. The lowest MAE was 0.49 D for Kane using post-DMEK TK, and the highest MAE was 1.05 D for BUII using pre-DMEK TK. Most IOLup1D formulae had lower MAEs than pre-DMEK K and TK formulae.

Conclusions: The IOLup1D Method should be used instead of pre-DMEK K and TK values for triple DMEK in FECD eyes. Using post-DMEK TK values for cataract surgery after DMEK provides better refractive accuracy than any of the three studied methods used for triple DMEK procedures.

Purpose: To evaluate the outcomes of endoscopy-assisted modified Weber-Ferguson's approach in the management of primary lacrimal sac tumors with extension into the neighboring tissues.

Methods: A retrospective interventional study was performed on all patients with lacrimal sac tumors treated with the endoscopy-assisted modified Weber-Ferguson approach between January 2010 and June 2022 at the Shanghai Ninth People's Hospital, China. Data assessed include demographics, clinical presentations, imaging features, surgical techniques, histopathology, adjuvant modalities of management, complications, and outcomes.

Results: A total of 13 patients were included in the analysis. Epiphora and palpable mass lesion were the presenting complaint in 84.6% (11/13) of the patients. Nearly half of the patients (46.1%, 6/13) were misdiagnosed as lacrimal duct obstruction. All the lacrimal sac tumors in the present series showed uneven enhancement on T1-weighted MRI imaging. Postoperatively, 84.6% (11/13) patients recovered well with excellent esthetics and were disease-free after a mean follow-up of 58.6 months. Two patients who underwent additional exenteration developed recurrence and succumbed (at 41 and 96 months follow up) while they were on palliative chemoradiation.

Conclusion: The endoscopic-assisted modified Weber-Fergusson surgical approach is effective in providing better visibility and accessibility to lacrimal sac tumors with extension into neighboring tissue.

Purpose: In this review, we aimed to investigate the literature on sex-specific prevalence of meibomian gland dysfunction (MGD) and to determine whether women or men are more at risk for MGD.

Methods: A search was conducted on PubMed using the terms: (Sex OR Gender OR prevalence) AND (Meibomian gland).

Results: Twenty-four relevant studies on MGD prevalence were identified, including 10 population-based and 14 hospital-based studies. Among the population-based studies, five studies reported higher rates among men, three studies found no differences, and one study observed higher rates among women. In the hospital-based studies, 10 studies reported no difference, two found higher rates among men, and one found higher among women. In the reviewed literature, there was a considerable variation between studies in terms of quality, sample size, age ranges, diagnostic criteria.

Conclusions: While most of the population-based studies suggest a higher prevalence among men, the majority of clinic-based studies show no significant difference. Further research with larger samples and standardized criteria is needed to determine whether men are indeed more susceptible to MGD.