Progression Of Diabetic Retinopathy Research Articles

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation

BACKGROUND Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca2+/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs. AIM To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR. METHODS DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis. RESULTS Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group. CONCLUSION Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

Lipidomic studies revealing serological markers associated with the occurrence of retinopathy in type 2 diabetes

PurposeThe duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR.MethodsA total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi’an JiaoTong University were selected as the discovery set. One-to-one case–control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography–mass spectrometry (LC–MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry.ResultsThe discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients.ConclusionDisturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

Upregulation of HMOX1 associated with M2 macrophage infiltration and ferroptosis in proliferative diabetic retinopathy

The roles of immune cell infiltration and ferroptosis in the progression of proliferative diabetic retinopathy (PDR) remain unclear. To identify upregulated molecules associated with immune infiltration and ferroptosis in PDR, GSE60436 and GSE102485 datasets were downloaded from the Gene Expression Omnibus (GEO). Genes associated with immune cell infiltration were examined through Weighted Gene Co-expression Network Analysis (WGCNA) and CIBERSORT algorithm. Common differentially expressed genes (DEGs) were intersected with ferroptosis-associated and immune cell infiltration-related genes. Localization of cellular expression was confirmed by single-cell analysis of GSE165784 dataset. Findings were validated by qRT-PCR, ELISA, Western blotting, and immunofluorescence staining. As a result, the infiltration of M2 macrophages was significantly elevated in fibrovascular membrane samples from PDR patients than the retinas of control subjects. Analysis of DEGs, M2 macrophage-related genes and ferroptosis-related genes identified three hub intersecting genes, TP53, HMOX1 and PPARA. qRT-PCR showed that HMOX1 was significantly higher in the oxygen-induced retinopathy (OIR) mouse model retinas than in controls. Single-cell analysis confirmed that HMOX1 was located in M2 macrophages. ELISA and western blotting revealed elevated levels of HMOX1 in the vitreous humor of PDR patients and OIR retinas, and immunofluorescence staining showed that HMOX1 co-localized with M2 macrophages in the retinas of OIR mice. This study offers novel insights into the mechanisms associated with immune cell infiltration and ferroptosis in PDR. HMOX1 expression correlated with M2 macrophage infiltration and ferroptosis, which may play a crucial role in PDR pathogenesis.

Vitamin C alleviates hyperglycemic stress in retinal pigment epithelial cells.

Retinal pigment epithelial cells (RPECs) are a type of retinal cells that structurally and physiologically support photoreceptors. However, hyperglycemia has been shown to play a critical role in the progression of diabetic retinopathy (DR), which is one of the leading causes of vision impairment. In the diabetic eye, the high glucose environment damages RPECs via the induction of oxidative stress, leading to the release of excess reactive oxygen species (ROS) and triggering apoptosis. In this study, we aim to investigate the antioxidant mechanism of Vitamin C in reducing hyperglycemia-induced stress and whether this mechanism can preserve the function of RPECs. ARPE-19 cells were treated with high glucose in the presence or absence of Vitamin C. Cell viability was measured by MTT assay. Cleaved poly ADP-ribose polymerase (PARP) was used to identify apoptosis in the cells. ROS were detected by the DCFH-DA reaction. The accumulation of sorbitol in the aldose reductase (AR) polyol pathway was determined using the sorbitol detection assay. Primary mouse RPECs were isolated from adult mice and identified by Rpe65 expression. The mitochondrial damage was measured by mitochondrial membrane depolarization. Our results showed that high glucose conditions reduce cell viability in RPECs while Vitamin C can restore cell viability, compared to the vehicle treatment. We also demonstrated that Vitamin C reduces hyperglycemia-induced ROS production and prevents cell apoptosis in RPECs in an AR-independent pathway. These results suggest that Vitamin C is not only a nutritional necessity but also an adjuvant that can be combined with AR inhibitors for alleviating hyperglycemic stress in RPECs.

Relationship between macular perfusion and lesion distribution in diabetic retinopathy.

To assess the relationship between macular vessel density metrics and foveal avascular zone (FAZ) characteristics on optical coherence tomography angiography (OCTA) and lesion distribution in eyes with diabetic retinopathy (DR). Patients with DR who underwent both Optos ultrawidefield (UWF) pseudocolor imaging and macular OCTA (Cirrus Angioplex, 6 × 6 mm) were included in this cross-sectional observational study. The distribution of DR lesions was assessed by comparing each of the peripheral ETDRS extended fields (3-7) against their corresponding ETDRS field, hence eyes were defined as either having predominantly peripheral lesions (PPL) or predominantly central lesions (PCL). En face OCTA images from the superficial and deep capillary plexuses (SCP and DCP) were then analysed using Image J software. Perfusion density (PD), vessel length density (VLD), and fractal dimensions (FD) were calculated following binarization and skeletonization of the images. Out of 344 eyes, 116 (33.72%) eyes had PPL and 228 (66.28%) eyes had PCL. For all DRSS levels, VLD, PD, and FD were not significantly different between eyes with PPL and PCL. The FAZ in eyes with PPL, however, was found to be more circular in shape compared to eyes with PCL (p = 0.037). Although the presence of PPL has been associated with a higher risk for diabetic retinopathy progression, the macular perfusion is similar in eyes with PPL and PCL. The FAZ is more circular in eyes with PPL, but the clinical relevance of this difference remains to be defined.

Effect of High-Sucrose Diet on the Occurrence and Progression of Diabetic Retinopathy and Dietary Modification Strategies.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of diabetic retinopathy (DR). They mainly include hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, and plays a vital role in the pathological changes of DR. High-sucrose diets (HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF), cause plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. The early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies that we give, patients can change their poor eating habits in a timely manner to avoid theoretically avoidable retinopathy and obtain an excellent prognosis.

USP5 facilitates diabetic retinopathy development by stabilizing ROBO4 via deubiquitination

Ubiquitin-specific proteases (USPs) have been proved to play important roles in the progression of diabetic retinopathy. In this study, we explored the role of USP5 and its possible mechanisms in diabetic retinopathy development. Cell proliferation, apoptosis, inflammation and oxidative stress were determined using CCK-8 assay, EdU staining assay, flow cytometry, and ELISA, respectively. The mRNA and protein expression of ROBO4 and USP5 were measured through RT-qPCR and western blot, respectively. Co-IP and deubiquitination assay were conducted to evaluate the interaction between ROBO4 and USP5. The results showed that high glucose (HG) stimulation significantly led to HRPE cell damage as described by suppressing proliferation, and promoting oxidative stress, inflammation and apoptosis. ROBO4 was markedly increased in diabetic retinopathy plasma samples and HG-triggered HRPE cells. Depletion of ROBO4 could alleviate HG-caused HRPE cell damage. USP5 was also significantly elevated in diabetic retinopathy plasma samples and HG-triggered HRPE cells. USP5 overexpression aggravated HG-induced HRPE cell damage. USP5 stabilized ROBO4 through deubiquitination. Moreover, USP5 knockdown decreased ROBO4 expression to mitigate HG-triggered cell damage in HRPE cells. USP5 stabilized ROBO4 via deubiquitination to repress cell proliferation, and facilitate inflammation, cell apoptosis and oxidative stress in HG-treated HRPE cells, thereby promoting the development of diabetic retinopathy.

Parafoveal capillary density as a potential biomarker in the assessment of diabetic retinopathy progression

AbstractPurposeThe aim of this study was to assess longitudinal changes in retinal vessel density in diabetic patients using optical coherence tomography angiography (OCTA) to identify the most sensitive parameter for detecting retinopathy progression.MethodsPatients with diabetes mellitus were enrolled in this study. Each study subject underwent two imaging sessions, during which three OCTA images of the macular area and three images of the optic nerve head were obtained. The two sessions took place one year apart. The OCTA imaging was performed using an AngioVue device. Superficial vessel density was evaluated in the central 3 mm and parafoveal area, and the nonflow area was measured using the built-in automated AngioAnalytics software of the Optovue system.ResultsThis study included 78 eyes of 39 diabetic patients (age: 55.16 ± 13.73 years) with a mean of 7.70 ± 1.07 mmol L−1 HgA1c level at baseline. At the one-year visit, the eyes of the diabetic subjects had significantly lower superficial vessel density in the parafoveal macula compared to corresponding values at baseline (p < 0.05). There was no statistically significant difference between the baseline and one-year results for the other vascular density parameters and the foveal avascular zone (p > 0.05).ConclusionAt the one-year follow-up, we found that vessel density had decreased in the parafoveal ring in these patients, while there was no significant change in other vascular parameters. This result suggests that superficial parafoveal capillary density is the most sensitive OCTA parameter that can be used as a biomarker for diabetic retinopathy progression. None of the other vascular density parameters nor the foveal avascular zone were able to indicate the subtle changes in retinal microcirculation due to the progression of diabetic microvasculopathy.

Biochemical Changes in Anterior Chamber of the Eye in Diabetic Patients-A Review.

This article aims to provide a comprehensive review of the biochemical changes observed in the anterior chamber of the eye in diabetic patients. The increased levels of inflammatory markers, alterations in antioxidant defense mechanisms, and elevated levels of advanced glycation end products (AGEs) in the aqueous humor (AH) are explored. Additionally, the impact of these biochemical changes on diabetic retinopathy progression, increased intraocular pressure, and cataract formation is discussed. Furthermore, the diagnostic and therapeutic implications of these findings are presented. This study explores potential biomarkers for detecting diabetic eye disease at an early stage and monitoring its progression. An investigation of the targeting of inflammatory and angiogenic pathways as a potential treatment approach and the role of antioxidant agents in managing these biochemical changes is performed.

A Case of Rapidly Progressive Proliferative Diabetic Retinopathy in the Setting of Severe Anorexia Nervosa

Purpose: To report a case of rapidly progressive diabetic retinopathy in the setting of admission for severe anorexia nervosa. Methods: Case report Results: A 21-year-old female with type 1 diabetes mellitus and mild nonproliferative diabetic retinopathy of both eyes was admitted for severe anorexia nervosa with a BMI of 12.5 and hemoglobin A1c of 10.6. Three months after admission, the patient reported visual complaints and was found to have severe nonproliferative diabetic retinopathy in the right eye and proliferative diabetic retinopathy with vitreous hemorrhage in the left eye. She was lost to follow-up for 4 months, then presented to clinic with bilateral proliferative diabetic retinopathy and a tractional retinal detachment of the right eye. Conclusion: There is a potential relationship between severe eating disorders and rapid worsening of diabetic retinopathy. Patients with type 1 diabetes who have acute complications due to eating disorders should be evaluated by an ophthalmologist to monitor for rapid progression of retinopathy.

Comparative Analysis of Early Diabetic Retinopathy Detection: Enhanced Minimal CNN vs VGG Architecture on CLAHE- Preprocessed Retinal Images

Ocular impairment is one of the prominent problems affecting middle-aged individuals due to uncontrolled blood sugar levels, commonly known as Diabetic Retinopathy (DR). The small abnormalities in the retinal capillaries, called microaneurysms and intra retinal bleeding, are the initial symptoms of Diabetic Retinopathy. Clinically recognizing diabetic retinal disease is a time-consuming and difficult process due to limitations in resources and experienced doctors. Early detection is crucial in avoiding the progression of Diabetic Retinopathy, highlighting the importance of an automated DR detection method to identify symptoms in its early stages. In this paper, researchers developed an unfamiliar framework known as Enhanced Minimal Convolutional Neural Network (EMCNN) to classify Mild-DR and No-DR ophthalmic photos using a binary classification process. The proposed new model EMCNN is compared with the migration learning method using the existing framework VGG16 and VGG19 in terms of precision and effectiveness. Before being sent across the network, the fundus pictures underwent preprocessing using the Contrast Limited Adaptive Histogram Equalization (CLAHE) tactic. EMCNN is an experimental model that enjoys a minimum number of layers and batch normalization to minimize the training effort. The EMCNN model achieved 94.89% accuracy using 3100 image dataset which is a remarkable improvement when compared with VGG architectures since the VGG architecture is trained with millions of images.

Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study

PurposeTo examine the effects of GLP-1 agonists compared to SGLT-2 inhibitors on diabetic retinopathy. DesignRetrospective clinical cohort study using TriNetX (Cambridge, MA, USA), a federated electronic health records network comprising multiple healthcare organizations. MethodsPatients with an International Classification of Diseases, Tenth Revision (ICD-10) code of non-proliferative diabetic retinopathy and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with history of proliferative diabetic retinopathy prior to initiation of treatment were excluded. Rate of progression to proliferative diabetic retinopathy and rate of development of diabetic macular edema were compared between patients on GLP-1 agonists compared to those on SGLT-2 inhibitors. The groups were propensity score matched for age, gender, ethnicity, race, type of diabetes, and severity of non-proliferative diabetic retinopathy. Main outcomes included rate and relative risk of progression to proliferative diabetic retinopathy and risk of diabetic macular edema in the GLP-1 agonist group versus the SGLT-2 inhibitor group. ResultsA total of 6481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching. At 1 year and 3 years after initiation of therapy, a higher rate of progression of proliferative diabetic retinopathy was noted (RR: 1.26, CI 1.04-1.51, p=0.017 at 1 year, RR: 1.284, CI 1.1-1.499, p=0.002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of diabetic macular edema noted at 3 months (RR: 1.192, CI 1.059-1.276, p=0.002), 6 months (RR: 1.22, CI 1.13-1.32, p<0.001), 1 year (RR: 1.24, CI 1.15-1.33, p<0.001), and at 3 years (RR: 1.29, CI 1.21-1.38, p<0.001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. ConclusionsA higher rate of progression of proliferative diabetic retinopathy and risk of new-onset diabetic macular edema was observed in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors. It is important for clinicians to be aware of these potential effects and to consider the current retinopathy status when initiating treatment with newer hypoglycemic agents to ensure these patients are appropriately monitored for developing potential vision threatening complications.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = -0.06 (-0.12, -0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = -55.63 (-90.73, -20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.

Role of Optical Coherence Tomography Angiography in Predicting Risk of Progression of Diabetic Retinopathy

Purpose: To determine the role of Optical Coherence Tomography Angiography (OCTA)in predicting risk of progression of diabetic retinopathy. Study Design: Descriptive observational study. Place and Duration of Study: Jinnah Post graduate Medical Center, Karachi, from June 2022 to June 2023. Methods: Patients with type 1 or 2 diabetes were included. Base line investigations were done including Central subfield thickness and OCTA at first visit. Second visit was conducted at 6th month and patients were followed for 24 months.OCT images of poor quality, motion artifact, inaccurate partition of tissue layers and blurry images were excluded. Results: Among 97 enrolled patients, 88 cases finished the complete 24-months follow up. Out of 88 patients, 16 (18.18%) patients showed progression of diabetic retinopathy (DR), 9 (10.22%) patients developed DME, two showed both DR and DME .In univariate analysis, greater FAZ area, reduced FAZ circularity, Fractal dimension (FD) and vessel density (VD) of the deep capillary plexus (DCP) were significantly related to the advancement in DR. Among these, FAZ area, VD, and FD remained significant in the multivariate analysis. Whereas, only decreased VD and FD of superficial capillary plexus (SCP) were significantly related to advancement in DR and DME. Conclusion: Changes in OCTA parameters is significantly associated with progression of diabetic ocular complications including diabetic retinopathy and diabetic macular edema. High risk subjects can be identified by this method for more rigorous treatment.

Comparative Analysis of Early Diabetic Retinopathy Detection: Enhanced Minimal CNN Vs VGG Architecture on CLAHE- Preprocessed Retinal Images

Ocular impairment is one of the prominent problems affecting middle-aged individuals due to uncontrolled blood sugar levels, commonly known as Diabetic Retinopathy (DR). The small abnormalities in the retinal capillaries, called microaneurysms and intra retinal bleeding, are the initial symptoms of Diabetic Retinopathy. Clinically recognizing diabetic retinal disease is a time-consuming and difficult process due to limitations in resources and experienced doctors. Early detection is crucial in avoiding the progression of Diabetic Retinopathy, highlighting the importance of an automated DR detection method to identify symptoms in its early stages. In this paper, researchers developed an unfamiliar framework known as Enhanced Minimal Convolutional Neural Network (EMCNN) to classify Mild-DR and No-DR ophthalmic photos using a binary classification process. The proposed new model EMCNN is compared with the migration learning method using the existing framework VGG16 and VGG19 in terms of precision and effectiveness. Before being sent across the network, the fundus pictures underwent preprocessing using the Contrast Limited Adaptive Histogram Equalization (CLAHE) tactic. EMCNN is an experimental model that enjoys a minimum number of layers and batch normalization to minimize the training effort. The EMCNN model achieved 94.89% accuracy using 3100 image dataset which is a remarkable improvement when compared with VGG architectures since the VGG architecture is trained with millions of images

Identification of PDGFA as a Neutrophil-related Biomarker Linked to the Advancement of Diabetic Retinopathy through Integrated Bioinformatics Analysis.

The dysregulation of the innate immune system plays a crucial role in the development of Diabetic Retinopathy (DR). To gain an insight into the underlying mechanism of DR, it is essential to identify specific biomarkers associated with immune cell infiltration. In this study, we retrieved the GSE94019 and GSE60436 datasets from the Gene Expression Omnibus (GEO) database. By utilizing CIBERSORT, MCPcounter, and xCell algorithms, we conducted a comprehensive analysis of the immune cell infiltration landscape in DR. The limma package was employed to identify Differentially Expressed Necroptosis-related Genes (DENRGs). Subsequently, enrichment analysis was performed to investigate the potential functions of the DENRGs. To identify the core DENRGs, the CytoHubba plug-in in Cytoscape software was utilized. The expression levels of these core DENRGs were verified in an independent dataset. Our analysis identified 213 DENRGs, and among them, Platelet-derived Growth Factor subunit A (PDGFA) was identified as a core DENRG. Notably, the expression of PDGFA was found to be upregulated in DR, and this finding was further validated in the GSE102485 dataset. Additionally, the results of GSVA and GSEA revealed that in the high PDGFA group, there was activation of pathways related to inflammation and the immune system. Moreover, analysis of immune infiltration demonstrated a significant association between PDGFA gene expression and the infiltration levels of specific immune cells, including basophils, macrophages M1, macrophages, neutrophils, monocytes, NK cells, and B cells. The involvement of neutrophils in the development and progression of DR is suggested. PDGFA has emerged as a potential marker and is linked to the infiltration of immune cells in DR. These findings shed new light on the underlying mechanisms of DR.

Risk of diabetic retinopathy according to subtype of type 2 diabetes.

Type 2 diabetes is a heterogeneous disease that can be subdivided based on beta-cell function and insulin sensitivity. We aimed to investigate the presence, incidence and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes which included classical, hyperinsulinemic and insulinopenic type 2 diabetes based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy (DiaBase) we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared to classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the future risk of DR.

GnT-V-mediated aberrant N-glycosylation of TIMP-1 promotes diabetic retinopathy progression

BackgroundVascular endothelial growth factor (VEGF) signaling pathway plays an important role in the progression of diabetic retinopathy (DR). The glycosylation modification process of many key functional proteins in DR patients is abnormal. However, the potential involvement of abnormal N-glycoproteins in DR progression remains unclear.MethodsGlycoproteomic profiling of the vitreous humor was performed. The level of protein and N-glycoprotein was confirmed by Western blot and Lectin blot, respectively. The cell viability and migration efficiency were detected by CCK-8 and Transwell assay. Flow cytometry was conducted to analyze the level of cell apoptosis and reactive oxygen specie. Malondialdehyde, superoxide dismutase activity and VEGF content were detected by Enzyme linked immunosorbent assays. The interaction of metalloproteinase 1 (TIMP-1) with N-acetylglucosamine transferase V (GnT-V) was detected by GST pull-down. Hematoxylin and eosin staining and choroidal and retinal flat mount stained with fluorescein isothiocyanate-Dextran assay were used for functional research in vivo.ResultsWe found that N-glycosylation was up-regulated in DR rats and high glucose (HG)-induced human retinal pigment epithelium cell line ARPE-19. HG-induced inhibited the viability of ARPE-19 cells and promoted cell apoptosis and oxidative stress (OS), but these effects were reversed with kifunensine treatment, GnT-V knockdown and TIMP-1 mutation. Additionally, GnT-V binds to TIMP-1 to promote N-glycosylation of TIMP-1. Over-expression of GnT-V inhibited the viability of ARPE-19 cells and promoted cell apoptosis, OS and VEGF release, which these effects were reversed with TIMP-1 mutation. Interestingly, over-expression of GnT-V promoted retinal microvascular endothelial cells (RMECs) angiogenesis but was revered with TIMP-1 mutation, which was terminally boosted by VEGF-A treatment. Finally, knockdown of GnT-V relieved DR progression.ConclusionThe findings indicate that GnT-V can promote RMECs angiogenesis and ARPE-19 cells injury through activation VEGF signaling pathway by increasing TIMP-1 N-glycosylation level, which provides a new theoretical basis for the prevention of DR.

Role of hyperhomocysteinemia in the progression of diabetic retinopathy

: The aim of this study was to determine the role of hyperhomocysteinemia in the progression of diabetic retinopathy and to determine the association of hyperhomocysteinemia with various grades of diabetic retinopathy.Diabetic retinopathy is the most common ocular complication of Diabetes mellitus. Various studies have shown that mild elevations of homocysteine in plasma are associated with an increased risk of vaso-occlusive disease, thrombosis, and stroke.: A total of 97 patients who were diagnosed with diabetic retinopathy from October 2018 to September 2019 were included in our study. Written informed consent was taken from all the participants. Best corrected visual acuity (BCVA), anterior segment examination using slit lamp biomicroscopy examination(SLE), fundoscopy using indirect ophthalmoscope and using 90D lens on slit lamp was done in all patients. Serum homocysteine was assessed in all. The data was analysed using SPSS version 17.0. Results were expressed as mean, frequency and percentage. Out of 97 patients, mean serum homocysteine seen in mild non proliferative diabetic retinopathy, moderate non proliferative diabetic retinopathy, severe non proliferative diabetic retinopathy and proliferative diabetic retinopathy was 13.8 ± 0.33, 14.6 ± 0.44, 14.64 ± 0.41 and 15.78 ± 1.33 respectively.: In our study we found serum homocysteine levels was elevated in proliferative diabetic retinopathy when compared to non-proliferative diabetic retinopathy.