Expression of Long Non-Coding RNA (lncRNA) SNHG5 in Patients with Refractory Diabetic Macular Edema and Its Regulatory Mechanism.

BACKGROUND The aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME). MATERIAL AND METHODS Optical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro. RESULTS Patients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated. CONCLUSIONS SNHG5 correlates with the development of DME and is a potential target for therapy.

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

Assessment of Inflammation Biomarkers in Diabetic Macular Edema Treated with Intravitreal Dexamethasone Implant.

Purpose: To evaluate inflammation biomarkers in diabetic macular edema (DME) treated with intravitreal dexamethasone implant (Ozurdex®). Methods: This retrospective single-center study investigated 64 eyes of 64 patients with DME who were nonresponsive to prior antivascular endothelial growth factor and treated with intravitreal Ozurdex. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio were calculated. Visual acuity and optical coherence tomography markers, including hyper-reflective dots and subretinal fluid (SRF), were determined, and central retinal thickness was also evaluated monthly for 3 months. Results: The average age was 64.06 ± 7.81 (48-84) years. The baseline NLR and MLR were significantly higher in patients with better visual outcomes (P = 0.029 and P = 0.048, respectively). Better anatomical outcomes were observed in the presence of SRF (P = 0.027). No significant differences were observed in the rates of the presence of SRF and hyper-reflective points about the better functional outcome (P > 0.05). Conclusions: SRF as an imaging biomarker, and NLR and MLR as blood biomarkers, stand out as markers of inflammation and were found to be associated with better response to Ozurdex implantation in DME.

Rapid lipidomic profiling based on ultra-high performance liquid chromatography-mass spectrometry and its application in diabetic retinopathy.

Lipidomics aims to characterize lipid alteration in response to internal or external subtle perturbations in complex biological samples. Lipid abnormality is a major risk factor for many diseases. Large-scale lipidomic studies may offer new insights into the pathophysiological mechanisms of diseases, new opportunities in systems biology, functional biology, and personalized medicine. To this end, a highly efficient and stable lipidomic method is highly in demand. We herein present a rapid and relatively high coverage lipidomic profiling approach based on ultra-high performance liquid chromatography-mass spectrometry by comparing the performance of different chromatographic columns, optimizing the elution gradient and selecting an appropriate data acquisition mode of mass spectra. As a result, a total of 481 lipids were detected from 40 µL serum sample within 13 min, covering 20 common lipid (sub)classes. The developed method was well validated with satisfactory analytical characteristics in linearity, repeatability, stability, and lipid coverage. To show the usefulness, the method was employed to investigate serum lipid profiling of 43 subjects with mild diabetic retinopathy and 44 normal controls, and successfully defined the differential lipids related to diabetic retinopathy. We believe that this rapid method will be beneficial for lipidomic analysis of large-scale clinical samples.

Assessment of Circulating Biomarkers in Relation to Various Stages of Diabetic Retinopathy in Type 2 Diabetic Patients-A Cross Sectional Study.

AIM: The aim of this study is to examine the relationship between inflammatory markers, and diabetic retinopathy in type II diabetic patients. METHODS: The study was a cross-sectional study included 150 type 2 diabetic patients who were divided into 3 groups. 50 in each group are divided as Diabetic patients without retinopathy (DM, n=50), nonproliferative diabetic retinopathy patients (NPDR, n=50), proliferative diabetic retinopathy patients (PDR, n=50). All the patients were subjected to complete clinical examination and laboratory investigations, such as fasting and postprandial blood glucose, serum creatinine, lipid profile tests, glycosylated haemoglobin (HbA1c), fasting insulin, serum inflammatory markers (TNF-alpha, C-reactive protein) and serum VEGF. RESULTS: The study revealed from the multivariate analysis that age, duration and WHR (waist-hip ratio) are potent risk factors responsible for the risk of Diabetic retinopathy. Similarly, serum creatinine, CRP, TNF- alpha and VEGF are significantly higher in diabetic patients with retinopathy compared to diabetic patients without retinopathy. CONCLUSION: The study concluded that inflammation was associated with severe diabetic retinopathy in patients with well-controlled diabetes. A possible relationship was provided between the risk factors and biomarkers which are responsible for Diabetic retinopathy. Hence, modifying the risk factors risk and development of severe diabetic retinopathy can be reduced.

Prevalence and severity of diabetic retinopathy in patients attending the endocrinology diabetes clinic at Mulago Hospital in Uganda.

AIMS: The epidemiology for diabetic retinopathy (DR) has been well described in the western population. Countries in Sub-Saharan Africa have attempted to identify the prevalence of diabetic eye disease, however, there still remains a degree of paucity across the continent due to inadequacy in health system organisations and resource poor settings. We aimed to identify the severity and prevalence of DR and maculopathy of patients attending the diabetes clinic at Mulago Hospital, Kampala, Uganda. METHODS: A cross-sectional observational study of 44 patients who attended a diabetes clinic at Mulago Hospital in April 2016. Parameters measured included visual acuity (VA) using a Snellen chart, blood glucose (mmol/l) and blood pressure (mmHg). Screening for DR grading was carried out with indirect fundoscopy and retinal photograph. Only the highest graded eye of retinopathy of each patient was included. RESULTS: A total of 41 eyes from 41 patients were included. Of these patients 15 were male. The average age of patients was 50.4 years. Six eyes (14.6%) had a VA < 6/18. Prevalence of DR was 19.5% (8 eyes) and 14.6% (6 eyes) had maculopathy. Of all eyes 14.6% had sight-threatening retinopathy, which was 85.7% of total cases of retinopathy in our study. CONCLUSIONS: We observed a high prevalence of DR and maculopathy, particularly sight threatening retinopathy, considering the proportion of patients screened. There is a need for a co-ordinated diabetes screening service through integration of the diabetes clinic and eye clinic at Mulago Hospital to better identify and treat this sight-threatening condition.

Early Assessment of the Risk Factors for Diabetic Retinopathy Can Reduce the Risk of Peripheral Arterial and Cardiovascular Diseases in Type 2 Diabetes.

BACKGROUNDS: There is still a lack of consensus about how to assess the risk of peripheral arterial disease (PAD) and cardiovascular disease (CVD) in patients with diabetic retinopathy (DR). AIMS: We investigated the risk factors for DR and their association with PAD and CVD in patients with type 2 diabetes (T2D). METHODS: A total of 1,421 patients diagnosed with T2D participated in this study. DR stages were classified as non-DR, nonproliferative DR (NPDR), or proliferative DR (PDR). Logistic regression analysis was employed to analyze risk factors associated with DR. RESULTS: NPDR and PDR patients had higher systolic blood pressure (SBP) and higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than the non-DR group (p < 0.05). The prevalence of abnormal ankle-brachial index (ABI) in the non-DR, NPDR, and PDR groups was 7.00, 10.80, and 13.96%, respectively (p < 0.05) and the prevalence of peripheral arterial plaques was 68.48, 81.38, and 80.56%, respectively (p < 0.001). Logistic regression analysis showed that DR (vs. non-DR) was associated with peripheral arterial plaques (OR = 2.07), SBP ≥130 mm Hg (OR = 1.53) and levels of hemoglobin (Hb)A1c (OR = 2.11) and TC (OR = 1.42). CONCLUSION: PAD is commonly associated with NPDR and PDR. Hypercholesterolemia is an important risk factor for the development of PAD and CVD in patients with DR. Our results suggest that a routine ABI test, duplex ultrasonography, and obtaining a lipid profile for DR patients may help to reduce the occurrence of PAD and CVD.

Apolipoprotein A-I and B and Subjective Global Assessment relationship can reflect lipid defects in diabetic retinopathy.

OBJECTIVE: Elevated lipid levels increase complications of diabetic retinopathy (DR). Uncontrolled diabetes increases these complications and causes unintentional weight loss, indicating an apparently normal body mass index (BMI). Thus, it is easy to assume that patients with DR and a normal BMI have optimal lipid status. Apolipoprotein (Apo) A-I and Apo B levels differentially indicate serum lipid status in DR. Subjective Global Assessment (SGA) scores are associated with DR status. If SGA scores and serum Apo A-I and B levels are found to be interrelated, their relationship can reflect lipid defects in patients with DR despite apparently normal BMI. The aim of the present study was to investigate the possible relationship between serum Apo A-I and B levels and SGA scores of patients with DR. METHOD: This was a case-control study conducted from November 2011 to April 2014. Serum Apo A-I and B levels and SGA scores were calculated for 40 healthy controls, 48 individuals without DR, 49 nonproliferative DR cases, and 48 proliferative DR cases. Pearson's correlation analysis was applied between Apo A-I, Apo B, Apo B/Apo A-I ratio, and SGA scores. RESULTS: Negative correlation was observed between serum Apo A-I level (r = -0.567, P < 0.001) and positive correlation between serum Apo B level (r = 0.451, P < 0.001) and Apo B/Apo A-I ratio (r = 0.597, P < 0.001) with escalating SGA scores. CONCLUSION: To our knowledge, this is the first study to report a novel correlation between serum Apo A-I, Apo B and Apo B/Apo A-I ratio and SGA scores. SGA scores can help predict lipid abnormalities in patients with DR even when they have an apparently normal BMI.

Comparisons of microRNA expression profiles in vitreous humor between eyes with macular hole and eyes with proliferative diabetic retinopathy.

PURPOSE: MicroRNAs (miRNAs) are small noncoding RNAs which regulate the activities of target mRNAs. We compared the expression profiles of the miRNAs in the vitreous of eyes with macular hole (MH) to that in eyes with proliferative diabetic retinopathy (PDR). METHODS: Vitreous and whole blood samples were collected from four patients with MH and from four patients with PDR. We assayed for 168 miRNAs in the vitreous and serum samples by the microRNA PCR Panel method. RESULTS: The mean number of miRNAs expressed in the vitreous was 63 (55-69) in eyes with MH and 86 (65-117) in eyes with PDR. The mean number of miRNAs expressed in the serum was 162 (159-167) in the MH patients and 142 (115-160) in the PDR patients. Twenty-six miRNAs were expressed in the vitreous of both MH and PDR eyes. Although there was no significant difference in the levels of 20 of the 26 (73 %) miRNAs expressed in both MH and PDR eyes, six of 26 miRNAs (24 %) (hsa-miR-15a, hsa-miR320a, hsa-miR-320b, hsa-miR-93, hsa-miR-29a, and hsa-miR-423-5p) were expressed significantly more highly in PDR eyes. In addition, the mean fold changes of three miRNAs, hsa-miR-23a, hsa-miR-320a, and hsa-miR-320b, in the vitreous to serum were significantly higher in the PDR group than in the MH group. CONCLUSIONS: The expression of several miRNAs related to angiogenesis and fibrosis was expressed significantly higher in the vitreous of eyes with PDR. Further studies are needed to understand the role played by the miRNAs in the biological function of the eye.

Serum vascular adhesion protein-1 correlates with vascular endothelial growth factor in patients with type II diabetes.

AIMS: To study serum levels of soluble vascular adhesion protein (sVAP)-1 in type II diabetic patients with retinopathy. METHODS: Serum samples were obtained from 53 consecutive patients, including 14 cases with non-angiogenic ocular diseases, i.e., epiretinal membrane (ERM) and idiopathic macular hole (MH), 19 cases with age-related macular degeneration (AMD), and 20 cases with diabetic retinopathy (DR). Protein levels of sVAP-1, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay. Enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO) was also measured. RESULTS: Serum level of sVAP-1 showed a moderate correlation with SSAO activity in all cases. Patients with DR had higher levels of serum sVAP-1 than subjects with ERM and MH, or those with AMD; however, severity of DR is not related to the serum levels of sVAP-1. Serum sVAP-1 correlated positively with VEGF in patients with DR, but not in those with ERM and MH, or those with AMD. Neither soluble ICAM-1 nor VCAM-1 correlated with VEGF, even in subjects with DR. CONCLUSION: The current data demonstrate the elevated serum levels of sVAP-1 and correlation between sVAP-1 and VEGF in patients with type II diabetes.

Assessment of diabetic retinopathy by measuring retina-specific mRNA in blood.

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of blindness in adults. Early detection and treatment of DR has been shown to reduce the risk of visual loss by as much as 90%. At present, there are no blood tests to detect DR. Previous studies have demonstrated the presence of nucleic acids in blood and raised levels of these markers have been reported in many conditions. The aim of this study was to evaluate the circulating levels of retina-specific mRNA in the assessment of DR. AREAS COVERED: Blood samples were taken into PAXgene Blood RNA tubes from 89 diabetic patients and 19 healthy individuals. A reverse-transcription quantitative real-time PCR assay was used to measure circulating levels of mRNA for rhodopsin (Rho), retinal amine oxidase (RAO) and phosphodiesterase 6C (PDE6C). The results were normalized against mRNA for ß-actin and total RNA. While mRNA for Rho, RAO and ß-actin were detected in 100% of the subjects, PDE6C mRNA was only found in 60% of the individuals and melanopsin mRNA was not detected. When diabetic subjects were divided according to their DR status, significant differences were observed for Rho and RAO-Rho increased while RAO tended to decrease. The area under the curve ROC for Rho and Rho/RAO ratio to differentiate mild or no DR from significant DR (pre-proliferative and proliferative stages) were 0.756 and 0.823, respectively. EXPERT OPINION: These findings suggest that circulating mRNA may be useful in assessing DR.

Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on progression of diabetic neuropathy and other microvascular complications: multivariate epidemiological analysis based on patient background factors and severity of diabetic neuropathy.

AIMS: The goal of the study was to evaluate the efficacy of epalrestat, an aldose reductase inhibitor, on diabetic retinopathy and diabetic nephropathy, based on analysis of the results of the Aldose Reductase Inhibitor-Diabetes Complications Trial, a 3-year multicentre comparative clinical trial of conventional therapy (control group) and epalrestat therapy (epalrestat group) in Japanese patients with mild diabetic neuropathy. METHODS: The subjects of the study were patients enrolled in the Aldose Reductase Inhibitor-Diabetes Complications Trial for whom data for major patient characteristics, severity of diabetic neuropathy at the end of the study and time-courses of diabetic retinopathy and diabetic nephropathy were available (57 and 52 patients from the control and epalrestat groups, respectively). Progression of diabetic retinopathy/nephropathy (a primary endpoint) in relation to major patient characteristics, severity of diabetic neuropathy at the end of the study (assessed from the mean of z-scores in four neurological function tests) and epalrestat treatment were analysed using univariate analysis and multiple logistic regression analysis. RESULTS: Progression of diabetic retinopathy/nephropathy was significantly inhibited in the epalrestat group compared with the control group (odds ratio = 0.323, P = 0.014) and was dependent on the severity of diabetic neuropathy at the end of the study (odds ratio = 2.131, P = 0.025). CONCLUSIONS: Epalrestat prevented progression of diabetic neuropathy and retinopathy/nephropathy. The effect on diabetic retinopathy/nephropathy may have occurred indirectly because of the prevention of progression of diabetic neuropathy, in addition to the inhibitory action of epalrestat on aldose reductase.

Scanning laser edema index: a reliable tool to correlate with diabetic retinopathy and systemic risk factors?

To correlate Heidelberg Retina Tomograph (HRT) derived macular edema (DME) index with severity of diabetic retinopathy and systemic factors. A total of 300 diabetic patients were recruited for the study for each of them a value for the macular edema index was obtained using the HRT II. Patients' age, gender, duration and type of diabetes mellitus, latest HbA1c result and presence or absence of co-morbid factors (hypertension, ischemic heart disease, nephropathy) were recorded together with the stage of diabetic retinopathy. These were correlated with DME. Out of 300 patients, HRT defined macula edema was seen in 68 patients (22.6%). There is a wider and higher range (95% percentile) of macula edema index in the severe non proliferative diabetic retinopathy (NPDR) group. Independent samples t test showed significant difference between the severe NPDR group and no DR group (p<0.001), mild NPDR group (p<0.05) and moderate NPDR group (p<0.05). A higher macula edema index was also found to have a low degree of correlation with more advanced stages of retinopathy (r=0.310; p<0.001). Also nephropathy showed a strong and significant correlation with DME. Hypertension had moderately significant correlation with DME. This study found no correlation between ischemic heart disease and DME. HRT derived scanning laser edema index is a reliable objective tool to evaluate diabetic retinopathy and systemic risk factors.

Diabetic retinopathy screening: perspectives of people with diabetes, screening intervals and costs of attending screening.

AIMS: To obtain the views of people with diabetes about the provision of diabetic retinopathy screening services; and the interval of screening. METHODS: Between October 2009 and January 2010, people with diabetes attending diabetic retinopathy screening clinics across Wales were asked to complete a questionnaire comprising of two parts: the first asking about their health, diabetes history, demographic characteristics and views about the diabetic retinopathy screening service, and the second asking about the costs of attending the screening. RESULTS: The response rate was 40% (n = 621) from 1550 questionnaires distributed at diabetic retinopathy clinics, with 600 complete responses analysed. Respondents had a mean known duration of diabetes of 8.5 years (sd 7.8) and had attended for screening on average 3.2 times (sd 1.6) in the last 5 years. Sixty-eight per cent (n = 408) of respondents reported having their eyes screened approximately once a year. Eighty-five per cent (n = 507) felt that they should have their eyes screened every year. However, 65% (n = 390) of respondents would accept screening at 2- or 3-year intervals if medical evidence showed that it was safe. The reported personal costs incurred by respondents attending diabetic retinopathy screening were low. CONCLUSION: Our study suggests that people with diabetes undergoing diabetic retinopathy screening would accept a greater screening interval, provided that adequate clinical evidence and medical reassurance were given.

Methodology and early findings of the Diabetes Management Project: a cohort study investigating the barriers to optimal diabetes care in diabetic patients with and without diabetic retinopathy.

BACKGROUND: The Diabetes Management Project is investigating the clinical, behavioural and psychosocial barriers to optimal diabetes care in individuals with and without diabetic retinopathy. DESIGN: Prospective cohort. PARTICIPANTS: Two hundred and twenty-three and 374 patients without and with diabetic retinopathy, respectively. METHODS: All individuals underwent a comprehensive dilated eye test, anthropometric measurements, blood and urine samples, and psychosocial questionnaires. MAIN OUTCOME MEASURES: Good glycaemic control was defined as glycosylated haemoglobin < 7%, good blood pressure control as systolic and diastolic values ≤130 and 80 mmHg, respectively, and good diabetes control as glycosylated haemoglobin < 7% and blood pressure values ≤130 and 80 mmHg. RESULTS: Four hundred and one males (65.4%) and 212 females (34.6%) aged 26-90 years (mean age ± standard deviation = 64.6 ± 11.6) were examined. The median glycosylated haemoglobin for all participants was 7.5% (interquartile range = 1.7%). Average systolic and diastolic blood pressure values were 139.7 mmHg (standard deviation = 18.8) and 92.7 mmHg (standard deviation = 30.9), respectively. Initial data analyses indicate that over two-thirds of participants with diabetes have poor glycaemic control, which was worse in those with diabetic retinopathy compared with those without (76.3% vs. 49.3%; P < 0.001). Blood pressure control was similar for those with and without diabetic retinopathy, with almost a third (28.5%) of the total sample having poor blood pressure control. Overall, those with diabetic retinopathy had poorer diabetes control than those without (24.3% vs. 13.7%; P = 0.002). CONCLUSIONS: Our findings substantiate the implementation of the Diabetes Management Project, developed to assess factors associated with suboptimal diabetes care.

Screening for diabetes in unconventional locations: resource implications and economics of screening in optometry practices.

OBJECTIVES: Unconventional locations outwith general medical practice may prove opportunities for screening. The aim was to determine the resource implications and economics of a screening service using random capillary blood glucose (rCBG) tests to detect raised blood glucose levels in the "at risk" population attending high street optometry practices. METHOD: A screening service was implemented in optometry practices in North East England: the cost of the service and the implication of different screening strategies was estimated. RESULTS: The cost of a screening test was £5.53-£11.20, depending on the screening strategy employed and who carried out the testing. Refining the screening strategy to target those ≥40 years with BMI of ≥25 kg/m(2) and/or family history of diabetes resulted in a cost per case referred to the GP of £14.38-£26.36. Implementing this strategy in half of optometric practices in England would have the potential to identify up to 150,000 new cases of diabetes and prediabetes a year. CONCLUSIONS: Optometry practices provide an effective way of identifying people who would benefit from further investigation for diabetes. Effectiveness could be improved further by improving cooperation and communication between optometrists and medical practitioners.

Retina-specific mRNA in the assessment of diabetic retinopathy.

In a previous study we demonstrated the presence and diagnostic usefulness of circulating rhodopsin mRNA in the assessment of diabetic retinopathy (DR). In the present study we investigated three further retina-specific markers in blood to determine their suitability as markers of DR. The markers were RPE65, retinoschisin, and melanopsin. Whole blood was collected from diabetic patients and healthy controls into PAXgene Blood RNA tubes and RNA was extracted using the PAXgene Blood RNA System. Quantitative real-time PCR was used to quantify mRNA for RPE65, retinoschisin, and melanopsin. beta-actin mRNA was used for normalization. RPE65, retinoschisin, and beta-actin mRNA were detected in 100% of subjects; melanopsin was not detected in either controls or diabetic patients. Circulating RPE65 mRNA concentration was 63% higher in diabetic patients than in healthy individuals (P= 0.019), whereas retinoschisin showed no change between the two groups. Compared with healthy controls, circulating RPE65 mRNA concentration was higher in diabetics with no retinopathy (30%; P= NS), background DR (93%; P= 0.01), preproliferative DR (20%; P= NS), and proliferative DR (107%; P= 0.004). Compared with diabetics with no retinopathy, levels of RPE65 mRNA were also significantly higher (60%) in the presence of proliferative DR (P= 0.029). In contrast, levels of retinoschisin mRNA were lower in background DR (34%; P= 0.033), preproliferative DR (43%; P= 0.026), and proliferative DR (47%; P= 0.038) compared to that in diabetics without retinopathy. We conclude that not all retina-specific mRNA species are detectable in circulation (e.g., melanopsin). This may be related to differences in expression levels for the individual markers. Both RPE65 and retinoschisin were detectable and demonstrated contrasting trends in diabetics with and without retinopathy. In combination with rhodopsin, RPE65, and retinoschisin, mRNA may offer a useful tool in developing a blood test for DR.

Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes--role of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy.

BACKGROUND: The aim of the study is to demonstrate the participation of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: Twenty four women and 22 men with type 2 diabetes (mean age 63.97 +/- 9.00 years, mean duration of diabetes 12.56 +/- 6.87 years) were enrolled in the study. Serum concentrations of soluble forms of ICAM-1, VCAM-1 as well as IL-6 and TNF-alpha were evaluated in all study subjects. In 19 patients, simultaneous assessment of selected parameter levels in both serum and vitreous samples was performed. Vitrectomy was performed due to intravitreal hemorrhage, accompanied in some patients by traction retinal detachment. The control group consisted of 15 patients having undergone vitrectomy for reasons other than PDR. Tests were performed using the ELISA method. RESULTS: Serum and intraocular concentrations of sICAM-1, sVCAM-1, IL-6, TNF-alpha were considerably higher in study subjects with PDR than in controls. Simultaneously, a positive correlation was found between intraocular sVCAM-1 (r = 0.590, p = 0.007), TNF-alpha (r = 0.822, p < 0.001) concentrations and HbA(1)c levels. The above-mentioned dependence was not shown for sICAM-1 and IL-6 vitreous concentration. Local vitreous VCAM-1 level increase was also dependent on vitreous TNF-alpha concentration growth (r = 0.470, p = 0.043). No significant correlation was found between serum and vitreous levels of the selected parameters in the group of 19 patients with PDR. CONCLUSIONS: Increase in sICAM-1 and sVCAM-1 levels, as well as their correlation with high vitreous IL-6 and TNF-alpha concentrations in patients with PDR, seem to confirm the inflammatory-immune nature of this process. In diabetes, inadequate metabolic control remains an important risk factor in the development of PDR.

Low prevalence of retinopathy, but high prevalence of nephropathy among Maori with newly diagnosed diabetes-Te Wai o Rona: Diabetes Prevention Strategy.

AIMS/HYPOTHESIS: To describe the prevalence of retinopathy and microalbuminuria at diagnosis of diabetes in a predominantly Maori study population. METHODS: Biomedical assessment including photographic retinal examination was undertaken among 157 (68.9% of eligible) members of Maori families (3.3% non-Maori) diagnosed with diabetes during a community screening programme (n=5240) as part of a diabetes prevention strategy. RESULTS: Mean HbA1c of those with newly diagnosed diabetes was 7.8+/-1.5% with 34.4% having an HbA1c >/=8.0%. Retinopathy was present in 3 (1.7%) subjects, cataracts in 3.2%, microalbuminuria in 29.6% and albuminuria in 7.7%. After adjusting for covariates, only smoking was a risk factor for microalbuminuria/proteinuria (current and former smokers: increased 3.81(1.32-11.0) and 3.67(1.30-10.4) fold, respectively). CONCLUSIONS: The prevalence of retinopathy at diagnosis was lower than in previous studies, yet that of microalbuminuria/proteinuria remained high. The retinopathy data suggest that case detection for diabetes in the community may be improving, but that other strategies among those at risk of diabetes, including those promoting smoking cessation, will be needed to reduce the risk of renal disease among Maori with diabetes.

[The assessment of the correlation between vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), glycaemic control (HbA1c) and the development of the diabetic retinopathy in children with diabetes mellitus type 1]. / Ocena zwiazku pomiedzy naczyniowym czynnikiem wzrostu sródblonka (VEGF), czynnikiem martwicy nowotworu (TIF-alpha), interleukina 6 (IL-6), wyrównaniem metabolicznym (HbA1c) a rozwojem retinopatii cukrzycowej u dzieci z cukrzyca typu 1.

The aim of the work is to assess the correlation between HbA1c, VEGF, TNF-alpha, IL-6 and the development of diabetic retinopathy in children diagnosed with diabetes mellitus type 1. One hundred fourty nine children with long-standing diabetes mellitus type 1 were enrolled in the study. The patients were divided into two subgroups: children with retinopathy (Group 1; n=28) and children without retinopathy (Group 2, n=121). The control group consisted of 62 healthy children. All the examined children had VEGF, TNF-alpha and IL-6 measured in the blood serum using highly sensitive ELISA tests. Statistically significant higher blood serum levels of HbA1c, VEGF, TNF-alpha and IL-6 were found in the group 1 in comparison with the group 2. Children of the group 2 in relation to healthy controls showed statistically significant higher blood serum levels of VEGF, TNF-alpha and IL-6. Elevated levels of VEGF, TNF-alpha, IL-6, HbA1c in blood serum of children with diabetes mellitus type 1 detected before development of overt signs of diabetic retinopathy might indicate the possibility of the occurrence of changes in the eye shortly.