Current Eye Research最新文献

Purpose: Chronic inflammation plays an important role in the pathogenesis of choroidal neovascularization (CNV). This study aimed to investigate the effect of the CHF5074, a γ-secretase inhibitor, on angiogenesis in a laser-induced CNV model and elucidate its possible molecular mechanism.

Methods: Male C57/BL6J mice aged between 6 to 8 weeks were employed to set up a laser-induced model of CNV. Then, CHF5074 was injected intraperitoneally on the day after laser modeling, as well as on the second, third, and fourth days. Immunofluorescence staining was used to evaluate the retinal and choroidal complex. The markers used were CD31 for neovascularization and IBA1 for microglia staining in ocular tissue slices. Fundus fluorescein angiography on days 3d, 7d, and 14d analyzed neovascularization and leakage areas. Inflammatory indicators were examined by Western blot (WB) and enzyme-linked immunosorbent assay (ELISA). High-throughput whole-tissue sequencing of retinal choroids identified relevant cell pathways. Key regulatory factors modulated by CHF5074 were identified via WB. Co-culture of BV2 cells and human umbilical vein endothelial cells (HUVEC) were used to explore the function of CHF5074 on the inhibition of tube formation.

Results: CHF5074 significantly decreased CD31 expression in the choroid on 3d, 7d, and 14d post-laser modeling (p < 0.05) and decreased both neovascularization and leakage areas (p < 0.05). Additionally, CHF5074 significantly lowered TNF-α, IL-10, and IL-1β expression levels in the choroid (p < 0.05), as demonstrated by WB analysis and ELISA. High-throughput whole-tissue sequencing identified P38-MAPK, JNK, and Wnt signaling pathways associated with neovascularization. CHF5074 decreased P38 protein phosphorylation (p < 0.05) as confirmed by WB analysis. CHF5074 inhibited the tube formation of HUVECs co-cultured with LPS and ATP-treated BV2 cells.

Conclusion: CHF5074 significantly suppresses angiogenesis in laser-induced choroidal neovascularization models, suggesting its potential as a novel agent for preventing and treating CNV.

Purpose: To assess the relationship between angle kappa (apparent chord mu) and ocular parameters in cataract patients.

Methods: In this cross-sectional study, the data on apparent chord mu, age, axial length, anterior chamber depth, anterior and posterior mean keratometry, mean total keratometry, white-to-white, central corneal thickness and lens thickness were collected for consecutive cataract patients. Correlation (Pearson) between chord mu and the other ocular parameters was calculated. A stepwise backward multiple regression analysis was performed to identify the combination of ocular parameters strongly correlating to chord mu.

Results: Two thousand four hundred and sixty-four eyes (1232 patients) were included in this study. The mean age was 72.7 ± 12.7 years (18-97 years). Univariate analysis showed a significant positive correlation of chord mu to age (R = 0.06, p = .01), lens thickness (R = 0.12, p < .01), mean keratometry (R = 0.08, p < .01), and mean total keratometry (R = 0.08, p < .01). Whereas there was a significant negative correlation with white-to-white (R = -0.04, p = .03), axial length (R = -0.19, p < .01), and anterior chamber depth (R = -0.2, p < .01). Male gender (R = -0.04, p = .05) and central corneal thickness (R = 0.04, p = .06) were not significantly correlated. Multivariate stepwise backward regression analysis showed a combination of four factors (female sex, reduced axial length and anterior chamber depth and steep mean keratometry) significantly related to chord mu (angle kappa).

Conclusion: Female gender, reduced axial length and anterior chamber depth, and higher mean keratometry correlate to apparent chord mu (angle kappa) in cataract patients. These findings can help identify vulnerable patients who can have appropriate counseling on the prognosis of postoperative optical and visual outcomes.

Purpose: Our aim was to examine the expression of PAX6 and keratocyte-specific markers in human limbal stromal cells (LSCs) in congenital aniridia (AN) and in healthy corneas, in vitro.

Methods: Primary human LSCs were extracted from individuals with aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8). The cells were cultured in either normal-glucose serum-containing cell culture medium (NGSC-medium) or low-glucose serum-free cell culture medium (LGSF-medium). Analysis of PAX6 and keratocyte-specific markers was conducted using qPCR and Western blotting. The keratocyte-specific markers included Collagen I (COL1A1), Collagen III (COL3A1), Collagen V (COL5A1), α-smooth muscle actin (ACTA2), Aldehyde Dehydrogenase 3 Family, Member A1 (ALDH3A1), Keratocan (KER), Lumican (LUM), and CD34.

Results: PAX6 mRNA expression exhibited a significant decrease in AN-LSCs compared to LSCs in both NGSC- and LGSF-medium (p = 0.04; p = 0.014). There was a marked reduction in COL5A1 mRNA expression (p = 0.011), accompanied by notably higher ALDH3A1 and KER mRNA levels (p = 0.007; p = 0.013) in AN-LSCs compared to LSCs when using NGSC-medium. In LGSF-medium, AN-LSCs showed a significant increase in COL1A1 and COL5A1 mRNA expression compared to LSCs (p = 0.048; p = 0.002). Moreover, COL1A1 and α-SMA protein expression were significantly elevated in AN-LSCs compared to LSCs in LGSF-medium (p = 0.048, p = 0.008).

Conclusions: Our investigation affirms the altered expression of PAX6 and keratocyte-specific markers in AN-LSCs relative to healthy controls. Both NGSC- and LGSF-medium exerted distinct effects on both LSCs and AN-LSCs. The observed variations in PAX6 and keratocyte-specific marker expression in AN-LSCs may play a pivotal role in the development and progression of aniridia-associated keratopathy.

Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.

Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.6 µg/mL, 3 µg/mL, 6 µg/mL, 300 µg/mL, and 3000 µ/mL or its solvent or PBS. The surface expression of platelet activation markers GPIIb/IIIa and P-selectin was determined by multispectral imaging flow cytometry, which combines flow cytometry and fluorescence microscopy. Two different methods were used to examine the interaction of brolucizumab with platelets: 1) A cross-pretreatment experiment was performed with FITC-labeled brolucizumab and bevacizumab; 2) Resting and activated platelets were pretreated with brolucizumab or its solvent or PBS, followed by anti-brolucizumab antibody generated by rabbit immunization.

Results: Brolucizumab did not significantly affect platelet activation compared to solvent or PBS, across a range of concentrations. No significant upregulation of CD62P and no activation of the fibrinogen receptor (GPIIb/IIa) were observed in resting and TRAP-activated platelets. After pretreatment with PBS, the level of brolucizumab-FITC was significantly lower in comparison to bevacizumab-FITC (normalized MFI = 3.32, CI = 3.16-3.48 vs. normalized MFI = 7.19, CI = 7.04-7.35; p < 0.001). Both brolucizumab- and bevacizumab-FITC were downregulated after pretreatment with brolucizumab or bevacizumab compared to pretreatment with PBS. Antibodies against brolucizumab did not show any significant difference between pretreatment with brolucizumab and its solvent in resting and TRAP-activated platelets.

Conclusion: Brolucizumab does not appear to directly affect platelet activation or reactivity to thrombin receptor agonists. No platelet interaction was observed after increasing brolucizumab concentrations or anti-brolucizumab antibodies in resting and activated platelets. However, brolucizumab might be taken up in platelets.

Purpose: To evaluate the effectiveness and safety of topical netarsudil 0.02% in managing childhood glaucoma.

Methods: A literature search in the electronic databases of PubMed CENTRAL, Google Scholar, EMBASE, the Register of Controlled Trials, and Ovid MEDLINE from January 2017 to August 2023 using one or a combination of the following terms: "netarsudil," "rhopressa," "Rho-kinase," "pediatric glaucoma," "childhood glaucoma," "intraocular pressure" was conducted.

Results: Eight publications (four retrospective studies, one prospective study, and three case reports) were identified evaluating the outcomes of topical netarsudil in childhood glaucoma. Six publications were conducted in the United States, and two publications were conducted in India. Studies included a heterogeneous cohort of primary and secondary childhood glaucoma with a variable range of follow-up (1 week-26 months). The mean IOP reduction after the initiation of topical netarsudil 0.02% in childhood glaucoma patients varies from 0.8 ± 13.2 to 12.0 ± 0.0 mmHg. The most common ocular adverse event was conjunctival hyperemia, seen in 27 out of 82 eyes (32.9%), followed by corneal honeycombing/reticular epithelial edema, seen in 13 out of 82 eyes (15.9%).

Conclusion: Limited literature is currently available on using topical netarsudil in childhood glaucoma. However, in children with refractory glaucoma on maximum topical medications, netarsudil may serve as an adjunctive treatment option, potentially delaying the need for further surgical interventions in some patients. Careful corneal examination is needed before and after initiation of netarsudil treatment for early detection of corneal adverse events that may compromise the vision.

Purpose: Corneal neurotization (CN) is a novel, potentially curative surgical procedure for the treatment of neurothophic keratopathy (NK). Patients with severe NK can present with corneal opacification requiring optical keratoplasty, which would likely fail without a proper trophic support of corneal nerves in the recipient cornea.

Methods: This is a pilot study on 4 patients undergoing keratoplasty after CN. Pre- and postoperative data at 12, 24 months and at the last follow-up were collected for the examination of (i) best corrected visual acuity (BCVA), (ii) slit lamp examination and photograph acquisition with and without fluorescein staining, (iii) corneal aesthesiometry, (iv) in vivo confocal microscopy of the central cornea. Neurophysiological study of the corneal reflex before corneal graft and at last follow up was performed.

Results: Four female patients (47.25 ± 5.06 y.o.) underwent keratoplasty after CN (3 penetrating keratoplasty, 1 deep anterior lamellar keratoplasty). The mean interval between CN and keratoplasty was 22 (± 12) months. The mean graft survival time was 42 (± 25) months. Graft follow-up ranged from 72 to 132 months. At the final follow-up, BCVA was improved in 2 out of 4 patients. The mean corneal sensitivity was 11.9 ± 8.3 mm at last follow-up. In vivo confocal microscopy confirmed the presence of functioning nerves at the last follow-up in all patients. NK-related complications occurred in 3 eyes (2 persistent epithelial defect, 1 corneal melting). The former complication was successfully treated by autologous serum eye drops while the latter required repeated keratoplasty.

Conclusions: Keratoplasty is a viable strategy to improve visual acuity in patients with corneal opacity who underwent CN for the treatment of NK. Even in the presence of functioning corneal nerves before keratoplasty, surgeons should be aware of the increased rate of NK-related complications that could require the need for repeated procedure.

Purpose: This study aimed to assess and compare the retinal toxicity associated with silicone oil (SO) and perfluoropropane (C3F8) tamponade following vitreoretinal surgery for fresh rhegmatogenous retinal detachment (RRD), utilizing the office-based Diopsys^® NOVA^™ system for evaluation.

Methods: Patients who underwent vitreoretinal surgery for fresh RRD and had SO (group 1) or C3F8 (group 2) tamponade were included in a prospective analysis. Flicker full field electroretinography (ffERG) and pattern electroretinography (PERG) tests were performed at 6 months postoperatively.

Results: Postoperative best corrected visual acuity (logMAR) was significantly different in group 1 and group 2 patients, 0.48 ± 0.3 and 0.30 ± 0.2, respectively. No significant disparities were found in demographic variables. Flicker ffERG and PERG recordings revealed notable alterations in retinal function parameters in the group 1 compared to the group 2.

Conclusion: Our findings suggest a correlation between SO tamponade and retinal dysfunction, evidenced by office-based ERG measurements. The Diopsys^® NOVA^™ protocol offers clinical ease in assessing retinal function. Further controlled studies are essential to validate these findings and guide clinical practice effectively.

Purpose: To reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation.

Methods: This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay.

Results: The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7-2068) and 1027(453-2527), respectively], and were both significantly higher than the control group [(521.5(231.6-2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: -0.220 and p < 0.05, r: -0.252, respectively) and their DVD values (p < 0.001, r: -0.324 and p = 0.001, r: -0.299, respectively).

Conclusions: Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients.

Purpose: Proliferative vitreoretinopathy (PVR) can cause blindness and the pathogenesis is unclear. Transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) of RPE cells is vital. P53 protein 2 (ASPP2) was previously reported to inhibit EMT in PVR rats, but the specific mechanism is unveiled.

Methods: TGF-β was used to induce EMT in ARPE-19 cells, and evaluated by immunofluorescence and western blot. ARPE-19 cells were transfected with scrambled/ASPP2-lentivirus, followed by TGF-β treatment. After that, alterations of EMT and autophagy were measured by western blot and transmission electron microscopy. Moreover, TGF-β and ARPE-19 cells treated with scrambled/ASPP2-lentivirus were employed to establish the PVR model via intravitreal injection to SD rats, and retinal changes as well as EMT and autophagy activity were evaluated accordingly.

Results: ASPP2 expression was decreased during TGF-β-induced EMT in ARPE-19 cells. In vitro, EMT and autophagy was activated by TGF-β, which could be partly reversed by ASPP2 upregulation. In vivo, ASPP2 upregulation protected against structural and functional changes in PVR retinas. Additionally, expressions of EMT and autophagy markers in retinas were inhibited by ASPP2 upregulation.

Conclusions: ASPP2 upregulation inhibited the EMT and autophagy process caused by TGF-β in ARPE-19 cells. Correspondingly, upregulation of ASPP2 alleviated intraocular fibrosis and protected visual function in PVR rats.