Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Diabetic retinopathy is a common blinding complication in diabetic patients. Compared with conventional fundus color photography, fundus fluorescein angiography can dynamically display retinal vessel permeability changes, offering unique advantages in detecting early small lesions such as microaneurysms. However, existing intelligent diagnostic research on diabetic retinopathy images primarily focuses on fundus color photography, with relatively insufficient research on complex lesion recognition in fluorescein angiography images. This study proposed an adaptive multi-label classification model (D-LAM) to improve the recognition accuracy of small lesions by constructing a category-adaptive mapping module, a label-specific decoding module, and an innovative loss function. Experimental results on a self-built dataset demonstrated that the model achieved a mean average precision of 96.27%, a category F1-score of 91.21%, and an overall F1-score of 94.58%, with particularly outstanding performance in recognizing small lesions such as microaneurysms (AP = 1.00), significantly outperforming existing methods. The research provides reliable technical support for clinical diagnosis of diabetic retinopathy based on fluorescein angiography.
Diabetic Retinopathy/diagnostic imaging* ; Humans ; Fluorescein Angiography ; Microaneurysm/diagnostic imaging* ; Retinal Vessels ; Algorithms

This paper summarizes Professor SUN Yuanzheng's academic thought and clinical experience in treating diabetic retinopathy (DR) with yuan-primary and luo-connecting meridian-regulating acupuncture. Professor SUN considers that the fundamental cause of DR lies in visceral dysfunction, with stagnation in the ocular collateral vessels and impairment of the mysterious orifices being the core pathogenesis. He proposes the treatment model of "regulating viscera, unblocking ocular collaterals, and opening mysterious orifices" based on yuan-primary and luo-connecting meridian-regulating acupuncture. Yuan-primary and luo-connecting points are used to balance qi, blood, yin, and yang of the viscera. Baihui (GV20) is stimulated with transcranial repetitive acupuncture to activate the yang qi of the governor vessel and invigorate qi in the twelve meridians, improving systemic microcirculation. Combining this with stimulation of ocular areas, Fengchi (GB20), and periocular points, the stasis in the ocular collaterals are cleared and the mysterious orifices are unblocked, addressing both the root and manifestations of DR.
Humans ; Diabetic Retinopathy/physiopathology* ; Acupuncture Therapy/history* ; Meridians ; Acupuncture Points ; Qi

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

OBJECTIVE

To compare the frequency and severity of color vision defects between diabetes mellitus (DM) patients without retinopathy and those with mild non-proliferative diabetic retinopathy (NPDR), and to evaluate the relationship between these color vision defects and capillary blood glucose (CBG) levels.

METHODS

This was a cross-sectional, hospital-based study conducted over a seven-month period at the Ophthalmology Outpatient Department of Cardinal Santos Medical Center. Thirty-five (35) DM patients (70 eyes) aged 50 to 75 years with best-corrected visual acuity of ≥20/50 and no more than mild NPDR were included. Patients with moderate or severe NPDR, macular edema, optic nerve pathology, or significant cataracts were excluded. All participants underwent visual acuity testing, fundus examination, and color vision assessment using the Ishihara pseudoisochromatic plates and Farnsworth D-15 tests conducted under standardized lighting conditions. CBG was measured using the finger-prick method. Main outcome measures included the proportion and type of color vision defects, their association with DR classification, and CBG levels. Statistical analyses included descriptive statistics, the Fisher exact test, the Mann-Whitney U test for the Farnsworth D-15 Color Confusion Index (CCI), and Spearman correlation between CBG and CCI.

RESULTS

Tritan-type defects were the most common, accounting for 36.2%. Color vision defects were observed in 91.3% (64 eyes) of patients with no DR, while defects were seen in all eyes (100%) with mild NPDR (5 eyes). However, this difference was not statistically significant (p = 1.000). There was no significant correlation between CBG levels and color vision scores. Mean CCI scores were similar between groups (p = 0.394), indicating no substantial difference in defect severity.

CONCLUSIONS

Color vision defects may be more prevalent in early NPDR compared to no DR, but this difference was not significant in this sample. No correlation was found between CBG levels and color vision performance. Color vision testing may serve as a useful adjunctive screening tool for early diabetic retinal changes; however, further studies with larger sample sizes are necessary.

Human ; Color Vision Defects ; Diabetic Retinopathy

This case study describes Mrs. CS, a 57-year-old grandmother with a 3-year history of Type 2 Diabetes Mellitus (T2DM), who came from a diabetic family and presented with blurry vision and fatigue. She was also diagnosed as hypertensive last year. She reported discontinuing all prescribed medications for five months, relying instead on decoctions of the Philippine serpentina plant (Andrographis paniculata) and the insulin plant (Chamaecostus cuspidatus) for blood pressure and glycemic control due to budget constraints. An HbA1c test revealed hyperglycemia (7.5%). This case highlights the critical public health challenge of medication non-adherence in T2DM patients, particularly those influenced by traditional herbal remedies. It emphasizes the significant risks of relying on unproven therapies, the resulting poor glycemic control, and the potential for severe microvascular complications like diabetic retinopathy. The report emphasizes the urgent need for comprehensive patient and family education regarding evidence-based T2DM management, the dangers of unsupervised medication cessation, and the importance of professional medical consultation to integrate any complementary therapies safely.

Human ; Female ; Middle Aged: 45-64 Yrs Old ; Diabetes Mellitus, Type 2 ; Andrographis Paniculata ; Diabetic Retinopathy

OBJECTIVE

To assess the diagnostic accuracy of point-of-care screening using Medios™ Artificial Intelligence (AI) in the diagnosis of diabetic retinopathy (DR).

METHODS

This is a multi-center, cross-sectional, instrument validation study among adult Filipinos with Type 2 diabetes seen at Endocrine specialty clinics from May to November 2021. Retinal images were captured by a minimally trained nurse using the Remedio Fundus on Phone (FOP). Images were interpreted separately by the Medios™ AI and three retina specialists. The primary outcome measure is the accuracy of Medios™™ AI in diagnosing DR compared to retina specialists’ findings using sensitivity and specificity, predictive values, and likelihood ratios.

RESULTS

A total of 182 subjects with Type 2 diabetes were included in the study. The sensitivity and specificity of the Medios™ AI in diagnosing any DR were 73.68% (95%CI, 57.99-85.03) and 83.74% (95%CI, 79.35-87.35), respectively, compared with the retinal specialists’ findings using the same images. The positive and negative predictive values were 34.57% (95%CI, 25.12-45.41) and 96.47% (95%CI, 93.62-98.07). The positive and negative likelihood ratios were 4.53 (95%CI, 4.26 4.82) and 0.31 (95%CI, 0.26-0.38). The overall diagnostic accuracy of Medios™ AI in detecting DR was 82.69% (95%CI, 78.47-86.23).

CONCLUSION

The Medios™ AI system showed acceptable diagnostic accuracy when used as a point-of-care screening tool in detecting DR among patients with Type 2 diabetes seen at Endocrine specialty clinics. This technology can be a useful screening tool for endocrinologists as it is relatively inexpensive, safe, and easily performed. It can also shorten the lead time from screening to referral and intervention.

Human ; Diabetes Mellitus ; Diabetic Retinopathy

OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

OBJECTIVES: Long noncoding RNAs (lncRNA) play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy. This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions. METHODS: Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection (WoSCC). A total of 1 516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis. CiteSpace and VOSviewer were used to analyze publication countries, institutions, journals, authors, co-cited references, and key words. RESULTS: The number of publications in this field has shown a steadily increasing trend from 2012 to 2022, peaking in 2021. China has the highest number of publications, while the United States ranked highest in centrality. Nanjing Medical University was the most prolific institution. Liu Y was the most productive author, while Wang Y ranked first in co-citation frequency. Cell was the most frequently cited journal. The latest terms of burst key words were vascular remodeling, dysfunction, heart, target, suppress, and pulmonary arterial hypertension. CONCLUSIONS From 2012 to 2022, research on lncRNAs in angiogenesis-related diseases has grown significantly. China leads in publication volume, while the United States holds the most academic influence. Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.
Bibliometrics ; RNA, Long Noncoding/genetics* ; Humans ; Neovascularization, Pathologic/genetics* ; Neoplasms/genetics* ; Diabetic Retinopathy/genetics* ; Biomedical Research/trends* ; China ; Angiogenesis