Myopia is a major public health concern that poses a serious threat to vision. The combination of precise monitoring of changes in the choroidal structure and blood flow, along with early prevention and control through pharmacological intervention, represents a key direction in myopia research. In the present study, swept-source optical coherence tomography angiography was used to obtain dynamic assessments of wide-field choroidal thickness and blood flow in guinea pigs before and after form-deprivation (FD). The effects of brimonidine on refraction, axial length, choroidal thickness, and perfusion in guinea pigs with form-deprivation myopia (FDM) were assessed. In addition, the choroidal expression of nitric oxide synthase (NOS), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), transforming growth factor-beta1 (TGF-β1), and α-smooth muscle actin (α-SMA) was quantified. The choroidal changes observed in the guinea pigs with FDM showed spatial heterogeneity, with areas of lower baseline choroidal thickness and blood flow showing greater susceptibility to FD stimulation and exhibiting more significant reductions. Brimonidine significantly slowed refraction and axial elongation in the FDM guinea pigs and broadly alleviated choroidal thinning and hypoperfusion. At the molecular level, brimonidine markedly reduced the FD-induced elevated choroidal expression of NOS, nNOS, eNOS, TGF-β1, and α-SMA. Brimonidine showed anti-myopic effects by preserving choroidal thickness and perfusion in FDM guinea pigs, potentially through suppression of the abnormally elevated expression of NOS, TGF-β1, and α-SMA in the choroid. These findings offer new insights and therapeutic targets for pharmacological prevention and control of myopia.

Among children, retinoblastoma (RB) is the leading primary ocular tumor, and AXL emerges as a significant player in tumors. Our research showed AXL’s expression was elevated in clinical retinoblastoma tumors relative to normal retinas. This upregulation was further validated through analysis of the GEO database. In vitro, SGI-7079 (AXL inhibitor) reduced RB cell line growth in a manner that depended on time and concentration, resulting in G2/M phase accumulation and apoptosis, and suppressed the expression of the PI3K/AKT/mTOR pathway. In vivo, SGI-7079 suppressed xenograft tumor growth. In summary, the research indicates that SGI-7079 might become a therapeutic strategy for RB.

This study investigated the antitumor effects of BIX01294, a pharmacological inhibitor of euchromatic histone-lysine N-methyltransferase 2 (EHMT2), in retinoblastoma and explored the underlying mechanisms. EHMT2 expression was evaluated using Gene Expression Profiling Interactive Analysis (GEPIA), human retinoblastoma specimens, publicly available Gene Expression Omnibus (GEO) datasets, and cultured cell lines. Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. Cell cycle distribution and apoptosis were analysed by flow cytometry. RNA sequencing (RNA-seq), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were performed to investigate downstream molecular changes. An orthotopic xenograft model was established to assess the in vivo pharmacological effects of BIX01294. EHMT2 was upregulated in retinoblastoma tissues and in retinoblastoma cell lines. BIX01294 reduced EHMT2 expression, inhibited proliferation, induced apoptosis, and caused cell cycle arrest, accompanied by downregulation of cyclin A, cyclin-dependent kinase 2 (CDK2), cyclin B, and phosphorylated cell division cycle 2 (p-CDC2). Under the same 48 h treatment conditions, ARPE-19 cells showed minimal changes in viability and no obvious alterations in apoptosis or cell-cycle distribution, supporting a degree of pharmacological selectivity. Transcriptomic profiling and protein analysis indicated that BIX01294 treatment was associated with attenuation of mitogen-activated protein kinase (MAPK) signalling. In the orthotopic xenograft model, BIX01294 reduced tumour burden and Ki-67 staining. These findings support EHMT2 as a potential pharmacological target in retinoblastoma; however, additional mechanistic studies are required to define the causal link between EHMT2 inhibition and MAPK pathway modulation.

PURPOSE:This study aims to evaluate the effects of brimonidine eye drops and intravitreal administration in guinea pigs with form-deprivation myopia (FDM) and to analyze the ocular pharmacokinetics and irritation. METHODS:The experimental guinea pigs were randomized to the normal control, FDM, FDM brimonidine topical eye drops, and FDM intravitreal injection groups. The experiment period was 13 days. Changes in ocular refraction and axial length were monitored regularly. The ocular pharmacokinetics of brimonidine and its metabolite brimonidine-2,3-dione were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Ocular irritation was assessed by the Draize test, corneal fluorescein staining, and hematoxylin and eosin staining. RESULTS:Two administration methods of brimonidine equally inhibited the increase in refraction and axial length in FDM guinea pigs (P < 0.05). Pharmacokinetic analysis revealed significant and sustained accumulation of brimonidine in the iris and choroid. Brimonidine was preferentially distributed to the cornea, conjunctiva, and sclera when administered topically, and preferentially to the retina and vitreous when administered intravitreally. The total area under the curve values for retinal and scleral tissues demonstrated that continuous topical administration was 1.95 times and 1.36 times that of intravitreal administration, respectively. The concentration of brimonidine-2,3-dione was significantly lower than that of brimonidine. Brimonidine topical eyedrops had less ocular irritation. CONCLUSIONS:At the drug concentrations in this study, both topical and intravitreal brimonidine achieved sufficient ocular exposure to exert similar myopia-suppressing effects. Continuous topical administration can maintain higher drug concentrations in the retinal and scleral tissues with less eye irritation.

Phakic Intraocular Lens (pIOL) has been studied for correction of high myopia and myopic astigmatism long before the advent of laser refractive surgery. It offers excellent visual and refractive outcomes, but the inherited risk of intraocular surgery cannot be overlooked. The posterior chamber pIOL (PC-pIOL), designed to be placed in the ciliary sulcus, may offer additional advantages compared to its anterior chamber counterparts. Given the complexity of sulcus anatomy and individual variations, controversies exist regarding perioperative management, implant selection, and operative techniques, necessitating standardisation. Given the emergence of novel approaches and long-term clinical data, a panel comprising 19 international experts from 9 countries/territories was formed by the Academy of Asia-Pacific Professors of Ophthalmology (AAPPO) and the Asia-Pacific Myopia Society (APMS). The panel critically reviewed the subject and synthesised 58 consensus statements that aim to provide evidence-based, real-world practice recommendations for optimal outcomes in PC-pIOL surgery.

Retinoblastoma (RB), the most prevalent intraocular malignancy in children, severely threatens vision and survival, yet therapeutic strategies for recurrent or refractory RB remain limited. MTHFD2 (Methylenetetrahydrofolate Dehydrogenase 2), one of the key enzymes involved in mitochondrial one-carbon metabolism, is aberrantly overexpressed in multiple cancers. Elevated MTHFD2 expression correlates with poor prognosis in various malignancies, and its depletion significantly suppresses tumor invasiveness and induces programmed cell death. However, whether MTHFD2 contributes to RB progression remains largely unexplored. Here, we reported that MTHFD2 expression was markedly upregulated in RB tissues and cell lines (Y79, Weri-RB1). In vitro functional assays demonstrated that MTHFD2 overexpression suppressed apoptosis and enhanced RB cell viability, colony formation, whereas MTHFD2 knockdown promoted apoptosis and inhibited RB cell viability, colony formation. In terms of mechanism, RNA sequencing and KEGG analysis revealed that differentially expressed genes (DEGs) were significantly enriched in pathways related to tumorigenesis. Meanwhile, we further demonstrated that MTHFD2 drove tumor progression by activating the Notch signaling pathway. Additionally, In vivo studies confirmed that MTHFD2 downregulation suppressed tumor graft growth and reduced expression of tumor proliferation marker Ki67. Our findings validate the critical oncogenic properties of MTHFD2 in RB by sustaining cell proliferation and preventing apoptosis. The tumor-promoting effects of MTHFD2 are likely mediated via the Notch signaling cascade, highlighting its potential as a therapeutic target for RB treatment.

Chemotherapy resistance is the major cause of nasopharyngeal carcinoma (NPC) treatment failure. Tripartite motif-containing protein (TRIM) family members play important roles in tumor development and chemotherapy failure. Here, based on a screening analysis of 71 TRIM family members by qRT-PCR, we first confirmed that the TRIM11 levels were significantly higher in drug-resistant NPC cells than in non-drug-resistant NPC cells, and high TRIM11 expression predicted poor overall survival (OS) and progression-free survival (PFS). N(6)-Methyladenosine (m6A) was highly enriched in TRIM11 in NPC drug-resistant cells and enhanced its RNA stability. TRIM11 enhanced the multidrug resistance in NPC by inhibiting apoptosis in vitro and promoting cisplatin (DDP) resistance in vivo. TRIM11 associated with Daple and promoted Daple ubiquitin-mediated degradation in a p62-selective autophagic manner, further upregulating β-catenin expression to induce ABCC9 expression by directly binding to the ABCC9 promoter. TRIM11 may regulate NPC drug resistance by positively modulating the Daple/β-catenin/ABCC9 signaling pathway. Thus, TRIM11 may be a potential diagnostic marker and therapeutic target for chemoresistant NPC.

Retinoblastoma (RB) is the most common intraocular malignancy among children and presents a certain mortality risk, especially in low- and middle-income countries. Clarifying the molecular mechanisms underlying the onset and progression of retinoblastoma is vital for devising effective cancer treatment approaches. PRMT1, a major type I PRMT, plays significant roles in cancer development. However, its expression and role in retinoblastoma are still unclear. Our research revealed a marked increase in PRMT1 levels in both retinoblastoma tissues and Y79 cells. The overexpression of PRMT1 in Y79 cells promoted their growth and cell cycle progression. Conversely, the suppression of PRMT1 hindered the growth of Y79 cells and impeded cell cycle progression. Mechanistically, PRMT1 mediated the growth of Y79 retinoblastoma cells by targeting the p53/p21/CDC2/Cyclin B pathway. Additionally, the ability of PRMT1 knockdown to suppress cell proliferation was also observed in vivo. Overall, PRMT1 could function as a potential target for therapeutic treatment in individuals with retinoblastoma.

Background Meteorin (METRN) is expressed predominantly in the central nervous system (CNS), where it functions by regulating glial cell differentiation and promoting axonal elongation. Nonetheless, its function within tumors is still not well understood. In this study, we focused on investigating its expression across various cancers and delving deeper into how METRN expression correlates with prognosis and immune infiltration. Methods We explored METRN expression patterns in pan-cancers utilizing data obtained from the UCSC Xena and TCGA. In addition, analyses of survival and clinical association were conducted for tumors where METRN could affect the prognosis. Subsequently, nomogram models were constructed for sarcoma (SARC) and prostate adenocarcinoma (PRAD) to verify METRN's prognostic value in tumors. Furthermore, we also discussed the link between METRN and immune infiltration. As far as mechanisms are concerned, functional enrichment analysis was conducted to analyze the functional components and signaling pathways involved in METRN. Results This study found that METRN was abnormally expressed in various tumors, closely connected with the prognosis and clinical characteristics of several tumors, and had good prognostic value. Moreover, analysis of immune infiltration revealed that METRN interacts with multiple immune cells, with alterations in the immune microenvironment potentially influencing tumor prognosis. Enrichment analysis indicates that METRN may influence tumorigenesis and progression through immune-related pathways. Conclusion To sum up, our study demonstrates that METRN can be a prospective predictive biomarker in diverse cancer types and a promising target for cancer immunotherapy for pan-cancer.

PurposeTo establish and characterize a dry eye model in New Zealand rabbits by subcutaneous injections of scopolamine hydrobromide (SCOP).MethodsTwenty New Zealand male rabbits were injected subcutaneously SCOP for 14 consecutive days; subcutaneous saline was used as a negative control. The correlated clinical parameters of ocular surface dryness were detected in vivo using tear secretion and corneal fluorescein staining. The expression of IL-1 beta and TNF-alpha on the ocular surface and in lacrimal glands were analyzed by real-time PCR and western blot on the 14th day. The expression of Mucin-5 subtype AC (MUC5AC) was detected by Immunofluorescence staining in conjunctival tissue.ResultsThe SCOP-treated rabbits exhibited significantly decreased aqueous tear secretion and increased corneal fluorescein staining scores over time. Both the mRNA expression levels and the protein expression levels of IL-1 beta and TNF-alpha were significantly increased after SCOP treatment compared with those after saline treatment. The loss of conjunctival MUC5AC was found in the SCOP-injected rabbits. Some infiltrated inflammatory cells and atrophic acinar cells were observed in the lacrimal gland after SCOP treatment. The disordered structures of the ocular surface and lacrimal glands were also observed.ConclusionsThis study showed that repeated subcutaneous SCOP injections successfully elicited some of the typical dry eye symptoms commonly seen in humans.

Purpose:Validation of the feasibility of novel acoustic radiation force optical coherence elastography (ARF-OCE) for the evaluation of biomechanical enhancement of the in vivo model of keratoconus by clinical cross-linking (CXL) surgery.Methods:Twelve in vivo rabbit corneas were randomly divided into two groups. Both groups were treated with collagenase type II, and a keratoconus model was obtained. Then, the two groups were treated with CXL procedures with different irradiation energy of 15 J and 30 J (CXL-15 J and CXL-30 J, respectively). An ARF-OCE probe with an ultrasmall ultrasound transducer was used to detect the biomechanical properties of cornea. An antisymmetric Lamb wave model was combined with the frequency dispersion relationship to achieve depth-resolved elastography.Results:Compared with the phase velocity of the Lamb wave in healthy corneas (approximately 3.96 ± 0.27 m/s), the phase velocity of the Lamb wave was lower in the keratoconus region (P < 0.05), with an average value of 3.12 ± 0.12 m/s. Moreover, the corneal stiffness increased after CXL treatment (P < 0.05), and the average phase velocity of the Lamb wave was 4.3 ± 0.19 m/s and 4.54 ± 0.13 m/s after CXL-15 J and CXL-30 J treatment.Conclusions:The Young's moduli of the keratoconus regions were significantly lower than the healthy corneas. Moreover, the Young's modulus of the keratoconus regions was significantly higher after CXL-30 J treatment than after CXL-15 J treatment. We demonstrated that the ARF-OCE technique has great potential in screening keratoconus and guiding clinical CXL treatment.Translational Relevance:This work accelerates the clinical translation of OCE systems using ultrasmall ultrasound transducers and is used to guide CXL procedures.

Purpose:The purpose of this study was to investigate the antitumor effects of GSK-J4 on retinoblastoma, as well as its related biological functions and molecular mechanisms. Methods:The antitumor effect of GSK-J4 on retinoblastoma was evaluated by in vitro and in vivo assays. CCK-8, EdU incorporation, and soft agar colony formation assays were performed to examine the effect of GSK-J4 on cell proliferation. Flow cytometry was used to evaluate the effect of GSK-J4 on the cell cycle and apoptosis. RNA-seq and Western blotting were conducted to explore the molecular mechanisms of GSK-J4. An orthotopic xenograft model was established to determine the effect of GSK-J4 on tumor growth. Results:GSK-J4 significantly inhibited retinoblastoma cell proliferation both in vitro and in vivo, arrested the cell cycle at G2/M phase, and induced apoptosis. Mechanistically, GSK-J4 may suppress retinoblastoma cell growth by regulating the PI3K/AKT/NF-κB signaling pathway. Conclusions:The antitumor effects of GSK-J4 were noticeable in retinoblastoma and were at least partially mediated by PI3K/AKT/NF-κB pathway suppression. Our study provides a novel strategy for the treatment of retinoblastoma.

Retinal fundus imaging contributes to monitoring the vision of patients by providing views of the interior surface of the eyes. Machine learning models greatly aided ophthalmologists in detecting retinal disorders from color fundus images. Hence, the quality of the data is pivotal for enhancing diagnosis algorithms, which ultimately benefits vision care and maintenance. To facilitate further research in this domain, we introduce the Eye Disease Diagnosis and Fundus Synthesis (EDDFS) dataset, comprising 28,877 fundus images. These include 15,000 healthy samples and a diverse range of images depicting various disorders such as diabetic retinopathy, age-related macular degeneration, glaucoma, pathological myopia, hypertension retinopathy, retinal vein occlusion, and Laser photocoagulation. In addition to providing the dataset, we propose a Transformer-joint convolution network for automated eye disease screening. Firstly, a co-attention structure is integrated to capture long-range attention information along with local features. Secondly, a cross-stage feature fusion module is designed to extract multi-level and disease-related information. By leveraging the dataset and our proposed network, we establish benchmarks for disease screening and grading tasks. Our experimental results underscore the network’s proficiency in both multi-label and single-label disease diagnosis, while also showcasing the dataset’s capability in supporting fundus synthesis. (The dataset and code will be available on https://github.com/xia-xx-cv/EDDFS_dataset).

The purpose of this study is to quantitatively evaluate the differences in corneal biomechanics after SMILE and FLEx surgery using an acoustic radiation force optical coherence elastography system (ARF-OCE) and to analyze the effect of the corneal cap on the integrity of corneal biomechanical properties. A custom ring array ultrasound transducer is used to excite corneal tissue to produce Lamb waves. Depth-resolved elastic modulus images of the in vivo cornea after refractive surgery were obtained based on the phase velocity of the Lamb wave. After refractive surgery, the average elastic modulus of the corneal flap decreased (71.7 ± 24.6 kPa), while the elastic modulus of the corneal cap increased (219.5 ± 54.9 kPa). The average elastic modulus of residual stromal bed (RSB) was increased after surgery, and the value after FLEx (305.8 ± 48.5 kPa) was significantly higher than that of SMILE (221.3 ± 43.2 kPa). Compared with FLEx, SMILE preserved most of the anterior stroma with less change in corneal biomechanics, which indicated that SMILE has an advantage in preserving the integrity of the corneal biomechanical properties. Therefore, the biomechanical properties of the cornea obtained by the ARF-OCE system may be one of the essential indicators for evaluating the safety of refractive surgery.

This work aims to depth-resolved quantitatively analyze the effect of different stromal ablation amounts on the corneal biomechanical properties during small incision lenticule extraction (SMILE) using optical coherence elastography (OCE). A 4.5-MHz ultrasonic transducer was used to excite elastic waves in the corneal tissue. The OCE system combined with the antisymmetric Lamb wave model was employed to achieve a high-resolution, high-sensitivity, and depth-resolved quantitative detection of the corneal Young’s modulus. Eighteen rabbits were randomly divided into three groups; each group had six rabbits. The first and second groups underwent -3D and -6D SMILE surgeries, and the third group was the control group, respectively. Young’s modulus of the corneal cap and residual stromal bed (RSB) were both increased after SMILE, which shared the stress under intraocular pressure (IOP). Furthermore, the Young’s modulus of both the corneal cap and RSB after 3D SMILE group were significantly lower than that in the -6D group, which indicated that the increases in the post-operative corneal Young’s modulus were positively correlated with the amount of stromal ablation. The OCE system for quantitative spatial characterization of corneal biomechanical properties can provide useful information on the extent of safe ablation for SMILE procedures.

Retinoblastoma (RB) is an intraocular malignancy that is most common in children and rare in adults. Addressing novel biomarkers and therapeutic targets for RB to modulate tumor progression has become a challenge. The aim of the present study was to investigate the function of long non-coding RNAs (LncRNAs) LOXL1-AS1 in RB cell proliferation and metastasis. It was found that LOXL1-AS1 was overexpressed in RB tissues and cells. In order to evaluate cell viability and colony formation potential, the knockdown of LOXL1-AS1 has been established. Knockdown of LOXL1-AS1 was also inhibited cells migration and invasion. In addition, the proportion of cells in the G2/M phase of the sh-LOXL1-AS1 group increased significantly, and the proportion of cells in the sh-NC group decreased significantly. In the xenograft model of RB, the tumors in the sh-LOXL1-AS1 group grow slowly compared to the sh-NC group. Western blot analysis revealed that LOXL1-AS1 can regulate the progression of RB cells through MAPK signaling pathway in vitro and in vivo. These results indicated that LncRNA LOXL1-AS1 promotes proliferation, invasion and inhibits apoptosis of retinoblastoma by regulating MAPK signaling pathway, and might be expected to be a novel basis for clinical diagnosis and treatment.

Optical coherence elastography (OCE) is a novel technique developed in recent years to investigate the biomechanical properties of tissues, similar to optical coherence tomography angiography, a functional version of optical coherence tomography.OCE utilizes load excitation to detect the mechanical response of ocular tissues, facilitating quantitative analysis of stress-strain curves, Young's modulus, and other biomechanical indicators.It also generates two-dimensional/three-dimensional elastic maps of the tissues.With its noninvasive, high-resolution, real-time, rapid, and three-dimensional imaging capabilities, OCE provides both structural and mechanical information about ocular tissues, opening up new dimensions in ocular disease diagnosis and pathogenesis research.This article introduced the technical classification and research status of OCE, and highlighted its research progress in ophthalmology, including its applications in assisted refractive surgery design, keratoconus patient screening, assessment of corneal cross-linking surgery efficacy, cataract diagnosis and grading, measurement of retinal biomechanics, and research into myopia pathogenesis.The challenges and opportunities for clinical translation of OCE in ophthalmology were also discussed.

目的 探讨超高度近视患者行后巩膜加固术后眼底形态的变化.方法 选取2016年5月至2017年8月南昌市第一医院眼科医院收治的行后巩膜加固术的超高度近视患者11例21眼作为研究对象.术后随访24～39个月,检测并记录患者最佳矫正视力(BCVA)、眼轴长度、视盘面积、Bruch膜孔面积、γ区长度、中心凹距视盘颞侧边缘距离、视网膜厚度、脉络膜厚度以及近视性视网膜病变(血管旁病变、视网膜劈裂)情况等.结果 21眼术后末次随访BCVA(logMAR)为4.2～5.0(4.78±0.26),与术前比较差异无统计学意义(P＞0.05);末次随访眼轴长度为27.24～33.64(30.49±2.39)mm,与术前相比,术后眼轴增长(0.38±0.34)mm(P＜0.05).21眼术前及术后末次随访视盘面积分别为(2.99±0.96)mm2、(2.84±1.12)mm2(P＞0.05),Bruch膜孔面积分别为(7.79±6.65)mm2、(8.12±6.76)mm2(P＞0.05),γ区长度分别为(1.39±0.64)mm、(1.31±0.71)mm(P＞0.05),中心凹距视盘颞侧边缘距离分别为(4.59±0.74)mm、(4.57±0.64)mm(P＞0.05).与术前相比,术后末次随访21眼ETDRS各区域后极部视网膜厚度和脉络膜厚度变化差异均无统计学意义(均为P＞0.05).术后末次随访,21眼中16眼视网膜结构稳定或近视性视网膜病变减轻甚至消失,5眼出现新的近视性视网膜病变或原有病变加重.结论 超高度近视眼行后巩膜加固术后眼轴仍有增长,眼底形态维持稳定,手术能在一定程度上减轻球内牵拉力.

Purpose: To study the role of lysine-specific demethylase 1 (LSD1) in retinoblastoma (RB) growth and to determine whether the LSD1 inhibitor SP2509 can inhibit RB progression. Methods: We detected the levels of LSD1 in 12 RB tissue samples, two RB cell lines (Y79 and Weri-RB1), and a retinal pigment epithelium cell line (ARPE-19). Overexpression or knockdown of LSD1 was performed to examine the role of LSD1 in RB cancer cell survival. In vitro and in vivo experiments were conducted to detect the antitumor effect of SP2509, and the antitumor mechanism of SP2509 was examined by RNA sequencing and Western blot. Results: LSD1 is overexpressed in RB tissues and cells and increases RB cancer cell viability and colony formation ability. The LSD1 inhibitor SP2509 inhibits RB cell proliferation in vitro and in vivo. Treatment with SP2509 increases the levels of dimethylated histone 3 lysine 4 (H3K4me2) and inhibits the expression of β-catenin signaling pathway–related proteins in RB cells. Conclusions: We demonstrated that LSD1 is overexpressed in RB cells and promotes RB cell survival. The LSD1 inhibitor SP2509 exerted strong growth inhibition in vitro and in vivo, which was at least partially mediated by suppression of the β-catenin pathway.