The Impact of Blood and Urine Biomarkers on Age-Related Macular Degeneration: Insights from Mendelian Randomization and Cross-sectional Study from NHANES.

INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of blindness, affecting millions worldwide. Its complex pathogenesis involves a variety of risk factors, including lipid metabolism and inflammation. This study aims to elucidate the causal relationships between biomarkers related to these processes and AMD, leveraging Mendelian randomization (MR) and cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES). METHOD: We conducted a two-phase study, initially using MR to explore the causality between 35 biomarkers and various AMD subtypes, followed by observational analysis with NHANES data to validate these findings. RESULTS: MR analysis identified a protective role of TG and a risk factor role of HDL-C and CRP in AMD development. NHANES data corroborated these findings, highlighting a nuanced relationship between these biomarkers and AMD. Notably, lipid metabolism-related biomarkers showed stronger associations with early AMD, whereas CRP's significance was pronounced in late AMD. CONCLUSION: This comprehensive analysis, combining MR with NHANES data, reinforces the importance of lipid metabolism and inflammation in AMD's etiology. Future research should further investigate these biomarkers' mechanisms and their potential as therapeutic targets for AMD prevention and treatment.

Impact of 24-Hour Intraocular Pressure on Optic Nerve Fiber Layer Thickness in Patients with Early Diabetic Retinopathy.

Background: The optic nerve fiber layer, composed of ganglion cell axons within the ganglion cell layer, undergoes thickness changes due to diabetic retinopathy. However, the relationship between intraocular pressure (IOP) and optic fiber layer thickness remains unclear. Objective: To investigate the correlation between 24-hour intraocular pressure and optic nerve fiber layer thickness in patients with early diabetic retinopathy. Methods: This retrospective study collected 353 patients with early diabetic retinopathy from January 2019 to December 2021. They were categorized into the retinopathy group (n = 153) and the control group (n = 200). 24-hour IOP and optic fiber layer thickness were assessed, and the correlation between them was analyzed. Results: The observation group exhibited significantly higher 24-hour IOP compared to the control group (16.64 ± 2.58 vs. 15.63 ± 2.52 mmHg, P < .001). Notably, the thickness of upper, lower, nasal, temporal, and average optic nerve fiber layers in the observation group decreased significantly (P < .001). Pearson linear correlation revealed significant negative associations between 24-hour IOP and upper, nasal, temporal, and mean optic nerve fiber layer thickness (R2 = -0.277, -0.399, -0.344, and -0.489, P < .05). The upper, lower, nasal, temporal, and mean optic fiber thickness demonstrated diagnostic value for non-early diabetic retinopathy in type 2 diabetes patients (P < .05), with mean optic fiber thickness displaying the highest diagnostic potential (area under the curve: 0.843, 95% Confidence Interval: 0.803-0.884, P < .001). Conclusions: Thinning of the optic nerve fiber layer in early diabetic retinopathy patients holds predictive value for the condition and exhibits a negative correlation with 24-hour intraocular pressure.

Causal effect of immune cells, metabolites, cathepsins, and vitamin therapy in diabetic retinopathy: a Mendelian randomization and cross-sectional study.

Background: Diabetic retinopathy (DR) is a major microvascular complication of diabetes and a leading cause of blindness worldwide. The pathogenesis of DR involves complex interactions between metabolic disturbances, immune cells, and proteolytic enzymes such as cathepsins (CATs). Despite various studies, the precise roles of different CATs, metabolites, and vitamins in DR remain unclear. Method: In this study, we employed Mendelian Randomization (MR) to assess causal relationships using genetic instruments selected based on genome-wide association studies (GWAS). We employed two-sample and mediation MR to explore the causal effects between nine CATs, immune cells, metabolites, vitamins, and DR. Additionally, the study also incorporated data from the NHANES survey to explore the associated relationship between vitamins and DR. We utilized cross-sectional data from the NHANES to analyze the association between vitamin intake and diabetic retinopathy (DR), adjusting for potential confounders to strengthen the validity of our findings. Results: The MR analysis identified CAT H as a significant risk factor for both NPDR and PDR, with no evidence of reverse causality. Additionally, 62 immune cell traits were found to have causal relationships with NPDR and 49 with PDR. Enrichment analysis revealed that metabolic pathways such as sphingolipid metabolism are crucial in DR progression. Vitamins B6 and E were significantly associated with a reduced risk of PDR. Cross-sectional data indicated that vitamins B1, B2, B6, B12, and E progressively decreased with DR severity. Conclusion: This study is the first to identify CAT H as a key risk factor for DR, while vitamins B6 and E showed significant protective effects, particularly against PDR. These findings suggest that CAT H, along with vitamins B6 and E, could serve as therapeutic targets for DR. Further validation through larger, multi-center studies is recommended to enhance the accuracy and applicability of these findings.

LINC00488 Induces Tumorigenicity in Retinoblastoma by Regulating microRNA-30a-5p/EPHB2 Axis.

OBJECTIVE: LINC00488 confers oncogenic activity in the progression of some tumors. Hence, the target of the study was about to specify LINC00488-mediated network in retinoblastoma (RB). METHODS: LINC00488 expression was tested in RB clinical tissues. siRNA targeting LINC00488 or miR-30a-5p mimic was introduced into RB cell line (Y79) to observe cellular biological functions. The relationship between LINC00488, miR-30a-5p and EPHB2 was verified. Afterward, the role of miR-30a-5p involved in RB through targeted regulation of EPHB2 was probed in vitro and in vivo. RESULTS: LINC00488 was induced in RB tissue and cells. LINC00488 knockdown or miR-30a-5p upregulation depressed the malignant activities of Y79 cells. LINC00488 could sponge miR-30a-5p that targeted EPHB2. EPHB2, and EPHB2 overexpression counteracted miR-30a-5p restoration-induced inhibition of Y79 cell development in vitro and in vivo. CONCLUSION: LINC00488 induces tumorigenicity in RB by binding to miR-30a-5p to target EPHB2, which may offer a new clue of RB treatment from an lncRNA-miRNA-mRNA network.

The Optos 200Tx Scanning Laser Ophthalmoscope Application in Retinoblastoma Patients' Follow-Up.

Methods: A total of 1134 examinations with Optomap 200Tx were performed for 318 children who were clinically diagnosed with RB in the Ophthalmology Department of Tianjin Medical University Eye Hospital, China, between July 2015 and July 2017, and achieved stable disease lasting for more than 6 months after combined treatment. The children received examinations every 1-12 months (mean 4 months), initially at 31 months to 15 years of age (mean 51 months), and were given a full eye examination under anesthesia (EUA) immediately if recurrent tumor, recurrent vitreous seeding (VS), or recurrent subretinal seeding (SRS) was detected, or in the next follow-up visit if no abnormality was detected, and early treatment was performed when the lesion was confirmed. Results: Recurrence was detected in 4 children in the examination with Optomap 200Tx, including 2 cases of recurrent vitreous seeding (VS) and 2 cases of recurrent subretinal seeding (SRS), which were confirmed by EUA and well controlled after early treatment. Conclusion: The use of Optomap 200Tx in the long-term following up of patients with RB reduces the number of eye examinations under general anesthesia (EUA), increases the time between EUAs, and protects children from exposure to the adverse effects of general anesthetics. Optomap 200Tx can detect recurrent tumor and recurrent seeding, allowing for early treatment which produces better outcomes.

Analysis of the etiologies, treatments and prognoses in children and adolescent vitreous hemorrhage.

AIM: To determine the etiologies, treatment modalities and visual outcomes of vitreous hemorrhage (VH; range from birth to 18y). METHODS: A total of 262 eyes from 210 patients between January 2010 and September 2016 were included. All children underwent an appropriate ocular and systemic examination. Data collected included demographics, clinical manifestations, details of the ocular and systemic examination, management details, final fundus anatomy and visual acuity (VA). RESULTS: The most common etiologies were non-traumatic VH (64.89%), most of which were due to retinopathy of prematurity (ROP; 37.10%); while traffic accidents, including 16 (21.00%) eyes, was the most common ocular traumas. Surgery, performed in 143 (54.58%) eyes, was the most common management modality. The initial mean baseline visual acuity was 2.77±0.21 logarithm of the minimal angle of resolution (logMAR) in children and adolescent with traumatic VH, which was significantly improved to 2.15±1.31 logMAR (P<0.05). CONCLUSION: VH in children and adolescent has a complicated and diverse etiology. ROP is the primary cause of non-traumatic VH, which is the most common etiology. Appropriate treatment of traumatic VH is associated with obvious improvement in visual acuity. The initial VA is one of most important predictors of outcome.

Stacking-Engineered Heterostructures in Transition Metal Dichalcogenides.

The layer-by-layer assembly of 2D transition metal dichalcogenide monolayer blocks to form a 3D stack, with a precisely chosen sequence/angle, is the newest development for these materials. In this way, one can create "van der Waals heterostructures (HSs)," opening up a new realm of materials engineering and novel devices with designed functionalities. Herein, a detailed systematic review of transition metal dichalcogenide stacking-engineered heterostructures, from controllable fabrication to typical characterization, and stacking-correlated physical behaviors is presented. Furthermore, recent advances in stacking design, such as stacking sequence, twist angles, and moiré superlattice heterojunctions, are also comprehensively summarized. Finally, the remaining challenges and possible strategies for using stacking engineering to tune the properties of 2D materials are also outlined.