Deficient Autophagy Contributes to the Development of Diabetic Retinopathy

2020 ◽  
Author(s):  
Jacqueline M. Lopes de Faria ◽  
Marcella Neves Dátilo
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Cell Survival ◽  
Nutrient Recycling ◽  
Degradation Process ◽  
Microvascular Endothelial Cells ◽  
Diabetic Patients ◽  
Autophagic Flux ◽  
Retinal Glial Cell

Autophagy is a self-degradation process essential to maintain intracellular homeostasis and cell survival, controlling elimination of pathogens, damage to organelles, and nutrient recycling to generate energy. Alterations in autophagic flux have been reported in the mechanisms of several diseases such as neurodegenerative diseases, cancer, diabetes mellitus, and its associated complications. Diabetic retinopathy (DR) is a microvascular complication of diabetes, affecting nearly 30% of diabetic patients. Several pathways are triggered and repressed in the development of DR, and autophagy showed to be relevant in the pathogenesis of this devastating complication. In this chapter, autophagy’s involvement in the development and progression of DR will be discussed, mainly in retinal pigmented epithelial cells and retinal microvascular endothelial cells, as well as in Müller cells—the more prominent retinal glial cell.

Abstract 516: Altered Autophagy Contributes to Endothelial Dysfunction in Human Diabetes Mellitus

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessica L Fetterman ◽  
Nir Flint ◽  
Monica Holbrook ◽  
Erika A Linder ◽  
Brittany D Berk ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Autophagic Flux ◽  
Compensatory Response ◽  
Patients With Diabetes ◽  
Lc3 Puncta

Diabetes is associated with increased oxidative stress and decreased nitric oxide (NO) bioactivity in the vasculature. Autophagy is a critical multistep pathway that eliminates oxidatively damaged proteins and organelles from the cell. Emerging evidence implicates impaired autophagy in a variety of non-vascular tissues that contributes to the pathogenesis of diabetes in experimental models. We hypothesized that impaired autophagy contributes to endothelial dysfunction associated with type 2 diabetes mellitus in humans. We measured vascular function and markers of autophagy in freshly isolated endothelial cells from patients with diabetes (n=41) and non-diabetic controls (n=41). Diabetes was associated with endothelial dysfunction characterized by lower brachial artery flow-mediated dilation. Endothelial cells from diabetic patients displayed no differences in LC3 puncta compared to those from controls but had higher levels of endothelial p62 (p=0.004), a protein that accumulates with reduced autophagic flux. In endothelial cells from controls, the autophagy inhibitor bafilomycin impaired eNOS activation, confirming that intact autophagy is necessary for NO signaling. Global activation of autophagy with spermidine reversed endothelial dysfunction in cultured endothelial cells exposed to high glucose (p=0.007). In regard to mechanism of impairment, the autophagy initiator rapamycin failed to improve eNOS activation in endothelial cells from diabetics. Further, expression of beclin-1, a key contributor to autophagosome formation, was similar in diabetics and controls, arguing against impaired initiation of autophagy. In endothelial cells from diabetics, blocking the terminal step of autophagy with bafilomycin led to a further accumulation of p62 (P=0.01), suggesting intact but insufficient levels of autophagy. Lamp2a, which facilitates the merger of autophagosomes and lysosomes, was higher in diabetic cells, possibly reflecting a compensatory response to reduced flux. Collectively, these findings provide evidence for inadequate autophagic flux in endothelial cells from diabetic patients that contributes to endothelial dysfunction and may be a target for therapy of diabetic vascular disease.

scholarly journals Knowledge, attitude and practice of diabetic retinopathy amongst diabetic patients in a tertiary care hospital of Jammu

2020 ◽  
Vol 8 (3) ◽  
pp. 836
Author(s):  
Pallavi Sharma ◽  
Bhavani Raina ◽  
Anuradha Bharti
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Tertiary Care ◽  
Diabetic Patients ◽  
Care Hospital ◽  
Ocular Complications ◽  
Attitude And Practice ◽  
Eye Disorders ◽  
Knowledge Practice ◽  
Knowledge Attitude And Practice

Background: Diabetes mellitus is a common metabolic disorder which is characterized by elevated blood sugar level. It is a major cause of blindness in our country, which is preventable and treatable, if healthy practice and knowledge regarding this disease is applied. The study was undertaken to assess the knowledge, attitude and practice of Diabetic Retinopathy, amongst diabetic patients attending eye OPD in GMC Jammu.Methods: 300 patients diagnosed with diabetes mellitus attending eye OPD, over a period of 10 months, in GMC Jammu, were incorporated in this study. Self administered questionnaires were used to assess knowledge, practice and attitude of diabetic retinopathy amongst the diabetic patient, after their due consent.Results: This study incorporated 300 diabetic patients out of which 168 (56%) were males and 132 (44%) were females. Most of the patients (70%) were aware of the fact that diabetes can cause eye disorders. 67.33% believed that they should go for regular eye check-ups. 79.33% agreed that timely intervention can delay the complications in diabetic eye disease.Conclusions: Diabetes can lead to serious ocular complications which can be prevented by appropriate awareness and optimistic attitude and good approach towards the disease.

scholarly journals Association of Retinopathy with Chronic Kidney Disease in Diabetes Mellitus

2018 ◽  
Vol 8 (3) ◽  
pp. 210-214
Author(s):  
Rushda Sharmin Binte Rouf ◽  
SM Ashrafuzzaman ◽  
Zafar Ahmed Latif
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Strong Association ◽  
Albumin Excretion Rate ◽  
Cross Sectional Study ◽  
Fundus Photography ◽  
Diabetic Patients ◽  
Cross Sectional

Background: Diabetic retinopathy (DR) and nephropathy are two major complications of diabetes mellitus carrying significant morbidity and mortality. In this study DR was investigated in different stages of chronic kidney disease (CKD) to find out possible association of these two devastating complications.Methods: This cross-sectional study was conducted in 150 diabetic patients having CKD in BIRDEM. CKD was defined as estimated glomerular filtration rate (eGFR) of <60ml/min/1.73m2and/or urinary albumin excretion rate (UAER) >30 mg/day in at least two occasions in 3 months apart. Retinopathy was assessed by direct fundoscopic examination and confirmed by color fundus photography. Severe DR (SDR) included proliferative diabetic retinopathy, severe non-proliferative DR and maculopathy; whereas microaneurysm regarded as non-severe retinopathy.Results: Majority (68%) of the respondents had some form of retinopathy (38.35% SDR and 29.65% nonsevere). There was strong association between different levels of albuminuria (UAER) and DR (p<0.0001). On the contrary DR did not correspond with stages of CKD (P=0.349). Hypertension (79.5%) and dyslipidaemia (59%) were common co-morbidities.Conclusion: This study concluded that DR prevalence was more in nephropathy along with significant association with UAER. Whereas different stages of CKD was not associated with stages of DR . This finding focused the necessity of regular retinal examination irrespective of the stage of renal involvement.Birdem Med J 2018; 8(3): 210-214

scholarly journals Histopathological evaluation of kidney disease in patients with diabetes mellitus

2021 ◽  
Vol 8 (2) ◽  
pp. 112-119
Author(s):  
Juju Raj Shrestha ◽  
Kashyap Dahal ◽  
Anil Baral ◽  
Rajani Hada
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Patients ◽  
Rapid Rise ◽  
Class Iii ◽  
Diabetic Kidney ◽  
Duration Of Diabetes

Introduction: Non diabetic kidney disease (NDKD), a treatable condition, is common in diabetic patients with atypical clinical presentations. Present study aimed to find out histopathological diagnosis of kidney disease in type 2 Diabetes mellitus with such presentations. Method: This was a hospital based cross sectional study conducted in Nephrology department, Bir hospital, Nepal from Aug 2019 to January 2021. Total 29 diabetic patients with atypical presentations, rapid rise of proteinuria alone (n=5), with microscopic hematuria (n=6), with impaired renal function (n=8) and rapid rise of creatinine with (n=8) or without (n=2) microscopic hematuria were included. The baseline information was recorded and kidney biopsy was performed. Result: The mean age of patients was 52.6±10.4 y and 22(75.9%) were male. Diabetic retinopathy (DR) was absent in 24(82.8%) patients. Presence of NDKD alone was in 6(20.7%) and superimposed on diabetic kidney disease (DKD) in 10(34.5%) with total NDKD in 16(55.2%) and isolated DKD in 13(44.8%) patients. Non diabetic kidney disease were glomerulonephritis 12(75%) with membranous nephropathy 4(25%) and IgA nephropathy 4(25%) patients. The significant difference between NDKD and isolated DKD was only the duration of diabetes < 5 y in 8(61.5%) of isolated DKD and ≥5 y in 13(81.2%) patients with NDKD (p=0.018). Diabetic retinopathy was absent in 6(100%) patients with isolated NDKD, 8(80%) of class III and 5(62.5%) of class IV DKD. Conclusion: Glomerulonephritis is the commonest NDKD in type 2 DM with atypical presentation and advance DKD (Class III & IV) is present even in absence of diabetic retinopathy and short duration of diabetes.

scholarly journals Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

2019 ◽  
Vol 19 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Jana Sajovic ◽  
Ines Cilenšek ◽  
Sara Mankoč ◽  
Špela Tajnšek ◽  
Tanja Kunej ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Vascular Endothelial Growth Factor ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Diabetic Patients ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and has been investigated as a candidate gene in a number of conditions, including diabetes and its microvascular complications (e.g., retinopathy and nephropathy). Several VEGF-related polymorphisms have been shown to contribute to nearly half of the variability in circulating VEGF levels in healthy individuals. Our aim was to assess the association between VEGF-related rs10738760 and rs6921438 polymorphisms and proliferative diabetic retinopathy (PDR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated the effect of these polymorphisms on VEGF receptor 2 (VEGFR-2) expression in fibrovascular membranes (FVMs) from patients with PDR. This case-control study enrolled 505 unrelated patients with T2DM: 143 diabetic patients with PDR as a study group, and 362 patients with T2DM of >10 years duration and with no clinical signs of PDR as a control group. Patient clinical and laboratory data were obtained from their medical records. rs10738760 and rs6921438 polymorphisms were genotyped using TaqMan SNP Genotyping assay. VEGFR-2 expression was assessed by immunohistochemistry in 20 FVMs from patients with PDR, and numerical areal density of VEGFR-2-positive cells was calculated. The occurrence of PDR was 1.7 times higher in diabetic patients carrying GA genotype of rs6921438 compared to patients with GG genotype, with a borderline statistical significance (OR = 1.7, 95% CI = 1.00 – 2.86, p = 0.05). In addition, A allele of rs6921438 was associated with increased VEGFR-2 expression in FVMs from PDR patients. However, we observed no association between AA genotype of rs6921438 nor between rs10738760 variants and PDR, indicating that the two polymorphisms are not genetic risk factors for PDR.

STUDY OF PREVALENCE AND CLINICAL PROFILE OF NEPHROPATHY AND RETINOPATHY IN TYPE 2 DIABETES PATIENTS AT TERTIARY CARE CENTER, UDAIPUR

2021 ◽  
pp. 6-8
Author(s):  
Yash Salil Patel
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Tertiary Care ◽  
Positive Family History ◽  
Diabetic Patients

Microvascular complications of Type 2 Diabetes Mellitus (T2DM), (retinopathy and nephropathy) have a similar etiopathogenetic mechanism besides genetic predisposition. Even though these two complications frequently co-exist, their frequency varies. The association of these two signicant complications and their coexistence needs a relook. To study prevalence of retinopathy and nephropathy in Type 2 diabetes mel Aim: litus. Comparison of diabetic retinopathy and nephropathy in Type 2 diabetes mellitus and its correlation of diabetic retinopathy and nephropathy with duration of illness and various risk factors that affects development, progression and severity of diabetic retinopathy and nephropathy. 100 diabetic patients were taken up for study for a period of one year meeti Methodology: ng the criteria for the present study. Detailed history was taken from patient and meticulous examination was done of all patients with special emphasis on renal and ophthalmic symptoms. Clinical data and investigation prole was tabulated. Statistical analysis was done. Among 100 patients, 22 had diabetic retinopathy. Among patients with diab Results & Conclusion: etic retinopathy, 68.18% patients had positive family history. Among 100 patients, 32 had diabetic nephropathy, mean FBS was 207 mg%, PPBS was 317.8 mg% and mean HbA was 9.2%. Among patients with diabetic retinopathy, mean FBS was 211 mg%, PPBS was 324.9 1c mg%, HbA was 9.5%. From this study it is found that diabetic nephropathy starts earlier than retinopathy. In this study 1c hypertension was found to accelerate progression into nephropathy and retinopathy.

ErbB2 Expression on Left Ventricular Epicardial Endothelial Cells and CD105+ Cells is Decreased in Patients with Diabetes Mellitus.

2021 ◽  
Author(s):  
Joanne T. deKay ◽  
Joshua Carver ◽  
Bailey Shevenell ◽  
Angela M. Kosta ◽  
Sergey Tsibulnikov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Cell Surface ◽  
High Glucose ◽  
Artery Bypass ◽  
Surface Expression ◽  
Left Ventricular ◽  
Cell Surface Expression ◽  
Erbb Receptors ◽  
Diabetic Patients

Abstract Background We investigated the cell surface expression of ErbB receptors on left ventricular (LV) epicardial endothelial cells and CD105+ cells obtained from cardiac biopsies of patients undergoing coronary artery bypass grafting surgery (CABG). Methods Endothelial cells and CD105+ non-endothelial cells were freshly isolated from LV epicardial biopsies obtained from 15 subjects with diabetes mellitus (DM) and 8 controls. The expression of ErbB recepotrs was examined using multiparametric flow cytometry. Human microvascular endothelial cells (HMEC-1) and LV epicardial CD105+ non-endothelial cells were used to determine the effect of high glucose on ADAM10-dependent cleavage of ErbB receptors. Results We found that diabetes mellitus (DM) and high levels of hemoglobin A1C are associated with reduced expression of ErbB2 on both endothelial cells and CD105+ non-endothelial cells. To determine if the expression of ErbB2 receptors is regulated by glucose levels, we examined the effect of high glucose in HMEC-1 and LV epicardial CD105+ non-endothelial cells, using a novel flow cytometric approach to simultaneously determine the total level, cell surface expression, and phosphorylation of ErbB2. Incubation of cells in the presence of 25 mM D-glucose resulted in decreased cell surface expression of ErbB2. We also found high expression of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) on both endothelial cells and CD105+ non-endothelial cells. Inhibition of ADAM10 prevented the high glucose-dependent decrease in the cell surface expression of ErbB2. Conclusions We suggest that high glucose depresses ErbB receptor signaling in endothelial cells and cardiac progenitor cells via the promotion of ADAM10-dependent cleavage of ErbB2 at the cell surface, thus contributing to vascular dysfunction and adverse remodeling seen in diabetic patients.

scholarly journals Association of serum vitamin D and parathormone levels in patients of type 2 diabetes mellitus with diabetic retinopathy

2017 ◽  
Vol 10 (2) ◽  
pp. 61
Author(s):  
Mohammad Shiblee Zaman ◽  
Md. Matiur Rahman ◽  
Subrata Kumar Biswas ◽  
Md. Mozammel Hoque ◽  
Khondakar Alwan Nahid
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Vitamin D Deficiency ◽  
Diabetic Patients ◽  
Control Serum ◽  
25 Hydroxy Vitamin D

<p>The present study was aimed to evaluate the association of serum 25-hydroxy vitamin D and parathormone in 46 patients of type 2 diabetes mellitus with diabetic retinopathy [non-proliferative, (n=27); proliferative (n=19)]. Twenty one diabetic patients without retinopathy were taken as control. Serum 25-hydroxy vitamin D and intact parathyroid hormone were measured by chemiluminescence microparticle immunoassay. Concentration of 25-hydroxy vitamin D differed significantly among groups (p=0.018) and it was significantly lower in proliferative diabetic retinopathy than no diabetic retinopathy (p=0.003). Logistic regression analysis revealed that vitamin D deficiency [25-hydroxy vitamin D &lt;20 ng/mL] was indepen-dently associated with development of diabetic retinopathy (p=0.007, OR 20.90, 95%CI 2.33-187.23). In conclusion, vitamin D deficiency is associated with diabetic retinopathy complicating type 2 diabetes mellitus.</p>

scholarly journals Study of aerobic bacterial conjunctival flora in patients with diabetes mellitus

2013 ◽  
Vol 5 (1) ◽  
pp. 28-32 ◽  
Author(s):  
D Karimsab ◽  
SK Razak
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Bacterial Flora ◽  
Diabetic Patients ◽  
Coagulase Negative Staphylococci ◽  
Ocular Infections ◽  
Patients With Diabetes ◽  
Conjunctival Flora ◽  
Normal Bacterial Flora

Introduction: Normal bacterial flora may be altered by a variety of factors. Objective: To study the aerobic bacterial conjunctival flora in patients with diabetes mellitus and to find its clinical significance by comparing the results to the conjunctival flora of non-diabetic subjects. Materials and methods: A total of 75 diabetic patients were included as cases and 25 nondiabetics as controls to compare the results. Specimens for the study of conjunctival flora were taken by rubbing sterile cotton-tipped swabs to the inferior palbebral conjunctiva. The conjunctival culture report of the patients with diabetic mellitus was compared to that of nondiabetic subjects. Results: Positive conjunctival cultures were seen in a higher percentage of patients with diabetes (unilateral and bilateral positive conjunctival cultures 34.66 % and 58.66 % respectively) compared to that in non-diabetic controls (unilateral and bilateral positive conjunctival cultures 24 % and 16 % respectively). Diabetics showed a higher proportion of coagulase negative staphylococci (45.33 %), compared to the non-diabetic group (16 %). Among the diabetic patients, positive conjunctival cultures were detected more frequently in those with diabetic retinopathy compared to those without retinopathy. A higher proportions of bilateral positive conjunctival cultures were seen in cases with proliferative diabetic retinopathy (38.63 %) in comparison to patients with no retinopathy and different stages of non-proliferative diabetic retinopathy. Conclusion: The conjunctival floral pattern with increased bacteria in diabetics is a predominant cause of many diabetes-related ocular infections. The presence of diabetic retinopathy is an indicator for increased colonization of conjunctiva, and its severity correlates with the severity of diabetic retinopathy. Nepal J Ophthalmol 2013; 5(9):28-32 DOI: http://dx.doi.org/10.3126/nepjoph.v5i1.7818

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