Background: Diabetic retinopathy (DR) urgently needs novel and effective therapeutic targets. Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel targets for diseases, but no systematic screening for DR has been performed.
Methods: Summary statistics of plasma protein quantitative trait loci (pQTL) were derived from two extensive genome-wide analysis study (GWAS) datasets and one systematic review, with over 100 thousand participants covering thousands of plasma proteins. DR data were sourced from the largest FinnGen study, comprising 10,413 DR cases and 308,633 European controls. Genetic instrumental variables were identified using multiple filters. In the two-sample MR analysis, Wald ratio and inverse variance-weighted (IVW) MR were utilized to investigate thecausality of plasma proteins with DR. Bidirectional MR, Bayesian Co-localization, and phenotype scanning were employed to test for potential reverse causality and confounding factors in the main MR analyses. By systemically searching druggable gene lists, the ChEMBL database, DrugBank, and Gene Ontology database, the druggability and relevant functional pathways of the identified proteins were systematically evaluated.
Results: Genetically predicted levels of 24 proteins were significantly associated with DR risk at a false discovery rate <0.05 including 11 with positive associations and 13 with negative associations. For each standard deviation increase in plasm protein levels, the odds ratios (ORs) for DR varied from 0.51 (95% CI: 0.36-0.73; P=2.22×10-5) for tubulin polymerization-promoting protein family member 3 (TPPP3) to 2.02 (95% CI: 1.44-2.83; P=5.01×10-5) for olfactomedin like 3 (OLFML3). Bidirectional MR indicated there was no reverse causality that interfered with the results of the main MR analyses. Four proteins exhibited strong co-localization evidence (PH4 ≥0.8): cytoplasmic tRNA synthetase (WARS), acrosin binding protein(ACRBP), and intercellular adhesion molecule 1 (ICAM1) were negatively associated with DR risk, while neurogenic locus notch homolog protein 2 (NOTCH2) showed a positive association. No confounding factors were detected between pQTLs and DR according to the phenotypic scan. Drugability assessments highlighted 6 proteins already in drug development endeavor and 18 novel drug targets, with metalloproteinase inhibitor 3 (TIMP) currently in phase I clinical trials for DR. GO analysis identified 18 of 24 plasma proteins enriching 22 pathways related to cell differentiation and proliferation regulation.
Conclusions:Twenty-four promising drug targets for DR were identified, including four plasma proteins with particular co-localization evidence. These findings offer new insights into DR's etiology and therapeutic targeting, exemplifying the value of genomic and proteomic data in drug target discovery.
Filamin C (FLNC) is a muscle protein encoded by the FLNC gene, which plays a crucial role as a muscle actin cross-linking center in skeletal and cardiac muscles, essential for maintaining cytoskeleton stability. Dominant autosomal mutations in the FLNC gene have been linked to various types of cardiomyopathies, myofibrillar myopathies (MFMs), and distal myopathies, representing rare, slowly progressive genetic muscle disorders typically starting in middle age. Evaluation of extraocular muscle strength in patients with FLNC gene mutations is relatively limited in current literature, with no clear documentation of its association with extraocular muscle weakness. This article reports a middle-aged male patient with ocular manifestations of incomplete closure of both eyelids, the outward turning of the right eye were completely limited, and the outward and inward turning of the left eye were completely limited. Following genetic testing, the patient was found to have a missense mutation in the FLNC gene (c.7423G>A:p.Val2475Ile). The patient also exhibits systemic manifestations including facial deformity and difficulty in squatting and standing. Combined with genetic testing results, the diagnosis was determined as acquired FLNC gene mutation-induced paralytic strabismus. This case illustrates the diverse phenotypes associated with FLNC variants, highlighting a novel mutation site in FLNC myopathy and the rare presentation of extraocular muscle weakness in the patient, expanding the clinical spectrum of FLNC gene mutation-related muscle disorders. It also emphasizes the importance of assessing the functional status of extraocular muscles during the examination and monitoring of FLNC myopathies.
Background: Research innovations inoculardisease screening, diagnosis, and management have been boosted by deep learning (DL) in the last decade. To assess historical research trends and current advances, we conducted an artifcial intelligence (AI)–human hybrid analysis of publications on DL in ophthalmology.
Methods: All DL-related articles in ophthalmology, which were published between 2012 and 2022 from Web of Science, were included. 500 high-impact articles annotated with key research information were used to fne-tune alarge language models (LLM) for reviewing medical literature and extracting information. After verifying the LLM's accuracy in extracting diseases and imaging modalities, we analyzed trend of DL in ophthalmology with 2 535 articles.
Results: Researchers using LLM for literature analysis were 70% (p = 0.000 1) faster than those who did not, while achieving comparable accuracy (97% versus 98%, p = 0.768 1). The field of DL in ophthalmology has grown 116% annually, paralleling trends of the broader DL domain. The publications focused mainly on diabetic retinopathy (p = 0.000 3), glaucoma (p = 0.001 1), and age-related macular diseases (p = 0.000 1) using retinal fundus photographs (FP, p = 0.001 5) and optical coherence tomography (OCT, p = 0.000 1). DL studies utilizing multimodal images have been growing, with FP and OCT combined being the most frequent. Among the 500 high-impact articles, laboratory studies constituted the majority at 65.3%. Notably, a discernible decline in model accuracy was observed when categorizing by study design, notwithstanding its statistical insignificance. Furthermore, 43 publicly available ocular image datasets were summarized.
Conclusion: This study has characterized the landscape of publications on DL in ophthalmology, by identifying the trends and breakthroughs among research topics and the fast-growing areas. This study provides an efcient framework for combined AI–human analysis to comprehensively assess the current status and future trends in the feld.
Phacoemulsification technology is an advanced method for treating cataracts, the leading cause of blindness worldwide. Kashgar, located in the westernmost part of China, has extensive economic, cultural, and medical exchanges with Central Asia. Promoting the application of cataract phacoemulsification technology in Pakistan aims to improve the treatment outcomes for local cataract patients and reduce the disease's blindness rate. The project leverages Pakistan's existing medical resources and technological equipment, relying on Kashgar's geographical and medical advantages, combined with the actual situation and needs of local medical staff. Through conducting doctor training, sending instructors to assist with surgeries in Pakistan, and refining surgical procedures, the project successfully implemented cataract phacoemulsification technology, effectively enhancing the treatment success rate and patient satisfaction. During the implementation process, the project encountered some difficulties and challenges but overcame them through team cooperation and scientific management, achieving good results. Ultimately, the project formed the distinctive Kashgar model, bringing a boon to cataract patients in the Pakistan region and potentially offering a reference for the promotion of other medical technologies.
To investigate the inhibitory effect of bilberry extract on retinal pigment epithelial (RPE) cells oxidative damage and angiogenesis. Methods: ①Human RPE cells (ARPE-19) were divided into three groups，control group, model group and bilberry extract group. The model group was treated with 0.5mmol/L SIN-1 for 24 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract, followed by 0.5mmol/L SIN-1 for 24 hours. Cell viability was measured by CCK-8. Level of reactive oxygen species (ROS) was determined using flow cytometry.② Human umbilical vein endothelial cells (HUVEC) were divided into three groups，control group, model group and bilberry extract group. The model group was treated with 10ng/ml VEGF for 8 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract for 12 hours, followed by 10ng/ml VEGF for 8 hours. Cell migration and invasion were measured by wound healing assay and Transwell assay. Cell angiogenesis was determined by tube formation assay. Results: ① Bilberry extract（≤10ng/ml）had no obvious toxicity to ARPE-19 cells. SIN-1 treatment significantly reduced the viability of ARPE-19 cells, while incubation with 10ng/ml bilberry extract could restore to the normal level（p<0.001）. Therefore the following experiments were used by 10ng/ml bilberry extract. Meanwhile, bilberry extract could significantly reduce SIN-1-induced ROS levels in ARPE-19 cells（p<0.0001）. ② VEGF treatment significantly enhanced the migration and invasion of HUVEC, while incubation with 10ng/ml bilberry extract could weaken（p<0.001）. Meanwhile, bilberry extract could significantly inhibit VEGF-induced tube formation in HUVEC（p<0.0001）. Conclusion: Bilberry extract is a potential treatment for AMD, which has significant antioxidant and anti-angiogenic activities.
To investigate the inhibitory effect of bilberry extract on retinal pigment epithelial (RPE) cells oxidative damage and angiogenesis. Methods: ①Human RPE cells (ARPE-19) were divided into three groups，control group, model group and bilberry extract group. The model group was treated with 0.5mmol/L SIN-1 for 24 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract, followed by 0.5mmol/L SIN-1 for 24 hours. Cell viability was measured by CCK-8. Level of reactive oxygen species (ROS) was determined using flow cytometry.② Human umbilical vein endothelial cells (HUVEC) were divided into three groups，control group, model group and bilberry extract group. The model group was treated with 10ng/ml VEGF for 8 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract for 12 hours, followed by 10ng/ml VEGF for 8 hours. Cell migration and invasion were measured by wound healing assay and Transwell assay. Cell angiogenesis was determined by tube formation assay. Results: ① Bilberry extract（≤10ng/ml）had no obvious toxicity to ARPE-19 cells. SIN-1 treatment significantly reduced the viability of ARPE-19 cells, while incubation with 10ng/ml bilberry extract could restore to the normal level（p<0.001）. Therefore the following experiments were used by 10ng/ml bilberry extract. Meanwhile, bilberry extract could significantly reduce SIN-1-induced ROS levels in ARPE-19 cells（p<0.0001）. ② VEGF treatment significantly enhanced the migration and invasion of HUVEC, while incubation with 10ng/ml bilberry extract could weaken（p<0.001）. Meanwhile, bilberry extract could significantly inhibit VEGF-induced tube formation in HUVEC（p<0.0001）. Conclusion: Bilberry extract is a potential treatment for AMD, which has significant antioxidant and anti-angiogenic activities.
Iron ions are essential for normal metabolism, DNA synthesis, and cellular repair in corneal cells. Nevertheless, an excess of these ions can disrupt iron homeostasis, leading to cellular toxicity, damage, and death. Keratoconus, the most prevalent ectatic corneal disorder, is often marked by the Fleischer ring, which indicates an imbalance in iron homeostasis. A review of early studies on keratoconus and iron metabolism suggests that this imbalance may be a potential pathogenic mechanism contributing to the onset and progression of the disease. This article aims to provide a comprehensive overview of normal iron metabolism in the human body and cornea, highlighting the evidence of iron homeostasis imbalance in keratoconus. It also explores potential therapeutic strategies focused on maintaining iron homeostasis, thereby offering novel insights into the treatment of ectatic eye diseases.
Objective: To evaluate the vascular endothelial function in patients with ocular hypertension and primary open-angle glaucoma, and explore the role of circulating endothelial progenitor cells in this process. Methods: Ocular hypertension (OHT group), primary open-angle glaucoma patients (POAG group), and age- and gender-matched healthy subjects (control group) were included with 30 sample size in each group. All subjects were <65 years old and had no history of cardiovascular disease or cardiovascular risk factors. Routine physical examination, ophthalmic examination and biochemical detection were performed. Brachial artery flow mediated dilation (FMD) was measured using ultrasonic diagnostic system, and the number of circulating endothelial progenitor cells was measured by flow cytometry. Results: Compared with control group, FMD, endothelial progenitor cell count, plasma nitric oxide (NO) content decreased (P<0.05) in OHT group and POAG group, while there was no statistical significance in the comparison of indicators above between OHT group and POAG group (P>0.05). There were no statistical differences in cardiovascular risk factors among the three groups (P>0.05). Partial correlation analysis showed that the number of endothelial progenitor cells in the OHT group and POAG group was significantly positively correlated with FMD (r＝0.436, P＝0.013) and NO (r＝0.385, P＝0.036), and negatively correlated with baseline intraocular pressure (r＝0.347, P＝0.041). Conclusion: Patients with OHT or POAG have systemic endothelial dysfunction, and the mechanism may be related to reduced number of circulating endothelial progenitor cells. Promoting the mobilization of endothelial progenitor cells to improve endothelial function may be a new direction for clinical treatment of patients with OHT or POAG.
Cataract is one of the leading causes of blindness worldwide, accounting for 50 percent of blindness cases in low- and middle-income countries. With the increase in population aging, the number of cataract blindness cases in China is expected to reach 20 million by 2050. Low health expenditures, shortages of medical equipment and ophthalmologists, and high screening costs are still the main reasons why mass cataract screening is not possible in low- and middle-income countries. Artificial intelligence-assisted cataract diagnosis has the advantages of being convenient, low-cost, and able to be performed remotely, which is expected to reduce or even avoid cataract blindness. In this review, we will briefly summarize the research on automatic cataract diagnosis by artificial intelligence (AI) by combining optical images, fundus photographs, and swept source optical coherance tomography images.
AIM：To evaluate the feasibility of intravitreal injection of dexamethasone intravitreal implant Ozurdex? combined with ranibizumab by comparing with ranibizumab alone for treatment of macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: Clinical data of fifty-one eyes of 51 CRVO-ME patients who were admitted to the eye center of the Second People's Hospital in Foshan from January 2022 to June 2023 were observed . They were divided into two groups: the combination （COM） group (11 patients with consecutive monthly intravitreal ranibizumab and Ozurdex? injections) and the anti-vascular endothelial growth factor (anti-VEGF) group (40 patients with “3+PRN”intravitreal ranibizumab injections). Best corrected visual acuity(BCVA),central retinal thickness(CRT), treatment costs. RESULTS: After 3.5mo and 6mo treatment, the differences in BCVA and CRT were statistically significantboth in the COM and anti-VEGF groups comparing with those pre-treatment(P<0.05).After 3.5mo treatment, there was no statistically significant difference in BCVA(P=0.917), or self-payment costs(P=0.097)in the COM versus anti-VEGF groups, but with statistically significant difference in CRT(P=0.026) and total treatment costs (P<0.01),. After 6mo treatment, no significant differences (P<0.05) were noted in BCVA and CRT between the COM and anti-VEGF groups. Within 6 months of follow-up, the number of injections was (2.27 ± 0.47) times in the COM group and (3.78 ± 1.00) times in the anti-VEGF group, and the difference between the two groups was statistically significant (P<0.01). CONCLUSION: The combination of Ozurdex? and ranibizumab has been shown to be comparable effective with anti-VEGF alone model in the treatment of CRVO-ME. Combination therapy reduces the amount of intravitreal injections and relieves the patients’ financial burden.
