Joanna Adamiec-Mroczek

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

BackgroundThe aim of the study is to demonstrate the participation of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy (PDR).MethodsTwenty 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-α 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.ResultsSerum and intraocular concentrations of sICAM-1, sVCAM-1, IL-6, TNF-α 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-α (r = 0.822, p < 0.001) concentrations and HbA1c 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-α 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.ConclusionsIncrease in sICAM-1 and sVCAM-1 levels, as well as their correlation with high vitreous IL-6 and TNF-α 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.

Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: Analysis of vitreous samples.

PURPOSE To investigate the roles of endothelin-1(ET-1), TNF-alpha, IL-6 in the pathogenesis of proliferative diabetic retinopathy (PDR) in type 2 diabetes. METHODS Vitreous and blood serum samples were collected during vitrectomy from 19 patients with PDR and 15 patients who underwent vitrectomy for other reasons. The concentrations of ET-1, TNF-alpha, IL-6, vWF, sE-selectin were determined by ELISA. RESULTS Intraocular and serous concentrations of ET-1, TNF-alpha, IL-6, vWF, sE-selectin were higher in patients with PDR than in the control group. The vitreous ET-1/plasma ET-1 ratios the group of diabetic patients and in the control group were similar. Also TNF-alpha, IL-6 vitreous/plasma ratio were not statistically different between the analysed groups. Correlation between intraocular ET-1 and TNF-alpha concentrations in patients with PDR and between the increases in both factors in the vitreous and HbA(1)c concentration were shown. In the vitreous the increase in vWF depended on elevated levels of vWF in the serum. E-selectin concentration correlated with diastolic blood pressure. CONCLUSION These data provide evidence of the activation of the local synthesis of ET-1, TNF-alpha, IL-6 in PDR. The relationship between the increase in vitreous ET-1, TNF-alpha concentrations and HbA(1)c concentration is a important confirmation of the necessity to optimise diabetes treatment.

Proliferative diabetic retinopathy―The influence of diabetes control on the activation of the intraocular molecule system

AIMS Demonstrate the influence of type 2 diabetes control on the degree of retinal endothelial damage (vWF, E-selectin) and local increases in the concentrations of selected adhesion molecules (ICAM-1, VCAM-1, E-selectin) in proliferative diabetic retinopathy (PDR). METHODS Vitreous and serum samples were collected during vitrectomy from 19 patients with PDR and 15 patients who underwent vitrectomy for other reasons. Tests were performed using the ELISA method. RESULTS Serum and intraocular concentrations of ICAM-1, VCAM-1, E-selectin, vWF were considerably higher in the subjects with PDR than in the controls. In the vitreous, the increase in vWF depended on the elevated levels of vWF in the serum (r=0.905, p<0.001). E-selectin correlated with diastolic blood pressure (r=0.506, p=0.045). The concentrations of vWF and E-selectin in both samples were related to the significant increases in intraocular ICAM-1, ICAM-1, VCAM-1 in the serum of PDR patients. Increased VCAM-1 level in the vitreous correlated with the concentration of HbA(1)c (r=0.59, p=0.007). CONCLUSIONS Upon local and systemic damage to the endothelium there were significant increases in ICAM-1, VCAM-1, E-selectin. A significant positive correlation of VCAM-1 increase in the vitreous with HbA(1)c is an important argument for the influence of diabetes on immuno-inflammatory activation in the retinal microcirculation.

The Dry Form of Age-Related Macular Degeneration (AMD): The Current Concepts of Pathogenesis and Prospects for Treatment.

Age-related macular degeneration (AMD) is a disease that causes varying degrees of blindness, which afflicts millions of adults in their later years. Preliminary changes occur during normal aging, but in some individuals the pathology leads to the development of AMD. The pathology seems to be a mixture of biochemical, cellular, and molecular events. Lipofuscinogenesis and early drusen genesis are in the early stages of AMD and their inhibition or reversal would dramatically increase the quality of vision in elderly people. The disease is characterized by abnormal extracellular deposits, known as drusen, which accumulate along the basal surface of the retinal pigmented epithelium RPE. Widespread drusen deposition is associated with retinal pigmented epithelial cell dysfunction and degeneration of the photoreceptors. Recent studies have shown that drusen contain a variety of immunomodulatory molecules, suggesting that the process of drusen formation involves local inflammatory events, including activation of the complement cascade. Molecular pathways involved in the etiology of this disease and the potential prospects of its treatment will be presented on the basis of the results of the current studies.

Glucocorticoid receptor polymorphism in obesity and glucose homeostasis

Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

The Influence of Incretin Mimetics on Cardiovascular Risk Factors in Diabetes

The authors discuss the strategy of use of incretin hormones in type 2 diabetes treatment in the context of cardiovascular complications. The results of the phase III study on human GLP-1 (Glucagon-like peptide-1) analogue-liraglutide have been presented under common acronym LEAD (Liraglutide-Effect and Action In Diabetes). The liraglutide therapy improved glycemic control with low hypoglycemia risk and decreased glycated hemoglobin by an average 1,13%. Decreases in systolic pressure and significant body weight loss were observed. Not only did the index describing beta cells function HOMA-B improve but also did the ratio of insulin to proinsulin. Summing up, incretin hormones beneficially influence blood glucose level, moreover, their use decreases blood pressure and body weight which might indicate their positive influence on cardiovascular system in diabetic patients.

Intravitreal ocriplasmin: A breakthrough in the treatment of vitreomacular traction?

Vitreoretinal interface pathologies, such as vitreomacular traction syndrome, epiretinal membranes and macular holes are sight-threatening conditions and one of the important causes of vision defects and vision loss. To this date, vigilance with observation of how the vitreomacular traction resolves, or vitreoretinal surgery in more severe cases, were the only treatment options. Recent rapid progress in ophthalmology, especially in diagnostic and visualization techniques, provided better insight into the mechanisms taking place on the vitreoretinal surface, which enabled a more accurate selection of treatment options. Development of ophthalmic pharmacological procedures, such as treatment of vitreomacular traction syndrome with ocriplasmin, constitutes an innovative breakthrough in ophthalmology. The enzyme is a genetically engineered form of human plasmin, a component of blood coagulation cascade that has been envisioned for human therapy since 1950s. It has never been used for vitreolysis in ophthalmology before. The aim of this review is to analyze and compare therapeutic options for symptomatic vitreomacular adhesion and vitreoretinal traction, with particular emphasis on microplasmin. We reviewed the results of recent studies comparing ocriplasmin to other widespread treatment options, such as pars plana vitrectomy.

Coronary artery disease: new insights into revascularization treatment of diabetic patients

Diabetes mellitus is an independent cardiovascular risk factor, considered an equivalent of coronary artery disease in terms of prognosis. A history of acute coronary syndrome is a strong predictor of another coronary episode, and cardiovascular complications are the leading cause of mortality in diabetic patients. Many patients with coronary artery disease suffer from concomitant diabetes or pre-diabetes. There are 3 strategies of coronary artery disease treatment: conservative management, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). Since drug-eluting stents (DES) were developed, PCI has become one of the most widespread interventional cardiology procedures performed in Europe and worldwide. Among all coronary risk factors, diabetes mellitus remains the most important predictor of unfavorable outcomes of revascularization therapy. This paper reviews the current evidence regarding revascularization in diabetic patients, with particular emphasis on PCI. A systematic analysis of clinical trials of CABG and PCI, especially with DES, was conducted.

Topical Nonsteroidal Anti-inflammatory Drugs for Cystoid Macular Edema Prevention in Patients With Diabetic Retinopathy

C ATARACT SURGERY IS THE MOST COMMONLY performed ophthalmic procedure worldwide. Surgical outcomes in terms of postoperative visual acuity keep getting better owing to continuous technological progress in medical devices and instruments, as well as because of improvement of surgeons’ skills. However, cataract surgery in a diabetic patient may constitute a challenge even for a highly skilled surgeon. Metabolic disorders associated with the primary disease not only contribute to earlier development of cataract, difficulties in achieving intraoperative mydriasis, severe postoperative inflammatory response, and prolonged visual recovery, but also result in higher incidence of pseudophakic cystoid macular edema (CME). Diabetic patients are without doubt particularly predisposed to pseudophakic CME. This postoperative complication develops in approximately 4% of individuals with diabetes mellitus (DM) (risk ratio [RR] 1⁄4 13.5). However, this proportion may increase to 10%–12% in subjects with nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) and up to 20%–50% in individuals with preoperative diabetic macular edema (DME). Sadly, even a correctly performed surgical procedure does not guarantee full therapeutic success in these groups. A number of recently published studies demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) may play a role in pseudophakic CME prevention; some authors even postulated that owing to their partially overlapping mechanisms of action, NSAIDs should replace glucocorticoids in therapeutic protocols. But the observations published by Modjtahedi and associates seem to undermine this opinion. The choice of optimal therapy after cataract surgery in diabetic patients is crucial. These new