Impaired function of circulating CD34 CD45 cells in patients with proliferative diabetic retinopathy

Proliferative diabetic retinopathy is a consequence of retinal ischemia due to capillary occlusion resulting from damage to the retinal microvascular endothelium. Recent evidence suggests that high levels of bone-marrow derived circulating endothelial progenitor cells (EPCs) contribute to the pathological neovascularization of ischemic tissues and are a critical risk factor for the development of these complications. In the absence of a consensus definition of a circulating EPC and its surface markers in humans we evaluated the functional properties of CD34⁺ CD45⁻ endothelial colony forming cells (ECFCs) in patients with proliferative diabetic retinopathy (PDR). Higher levels of circulating CD34⁺ CD45⁻ cells were observed in patients with PDR compared to controls. However, ECFCs from patients with PDR were impaired in their ability to migrate towards SDF-1 and human serum, incorporate into and form vascular tubes with human retinal endothelial cells. The results from these pilot studies suggest that ECFCs from patients with PDR are mobilized into the circulation but may be unable to migrate and repair damaged capillary endothelium. This suggests that ECFCs may be a potential therapeutic target in the prevention and treatment of diabetic vascular complications.     

Dysfunction of circulating endothelial progenitor cells in type 1 diabetic rats with diabetic retinopathy

Purpose

To investigate the role of endothelial progenitor cell (EPC) in the pathogenesis of diabetic retinopathy (DR) in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) rats.

Methods

A total of 160 male Wistar rats (12 weeks old; 250–350 g) were randomly assigned into four groups (n?=?40 for each), including control (group 1, no treatment), T1DM1 (group 2, 1 month after 50 mg/kg of STZ, single i.p.), T1DM3 (group 3, 3 months after 50 mg/kg of STZ, single i.p.), T1DM6 (group 4, 6 months after 50 mg/kg of STZ, single i.p.). Enumeration of circulating EPC from peripheral blood was measured by flow cytometry. EPC from bone marrow of rats was cultured in vitro to evaluate its function of proliferation, adhesion, and migration activities. Plasma levels of vascular endothelial growth factor (VEGF) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay (ELISA). Retinal sections were imaged by light microscopy and a transmission electron microscope (TEM).

Results

The numbers of circulating EPC were significantly decreased in diabetic groups compared with the control group. Impaired proliferation, adhesion, and migratory activities of cultured EPC were observed in diabetic groups. There were significantly higher levels of plasma VEGF but lower levels of plasma NO in diabetic groups than those in non-diabetic controls. The significantly reduced thickness and obvious disorganized retinal cell layers were seen in T1DM DR rats. In the diabetic groups, we also found that T1DM rats developed telangiectatic vessels, vacuolar degeneration of ganglion cells, and thickened capillary basement membrane with capillary lumen stenosis in the retina. Significantly raised EPC numbers during DR formation and progression were also found.

Conclusions

The reduced numbers and impaired function of circulating EPC may contribute to the pathogenesis of DR in T1DM rats.     

Platelet activation in patients with diabetic retinopathy

To clarify the diabetic complications mediated by increased platelet activity, we undertook a study of the mean platelet component (MPC), as determined by an automated hematologic analyzer (ADVIA 120, Bayer). Prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen were also measured to investigate blood viscosity abnormalities. MPC was determined in 100 healthy controls and in 100 diabetic patients, the latter of which were subdivided into no diabetic retinopathy (DR) (n = 25), nonproliferative DR (n = 30), and proliferative DR (n = 45) groups. The mean MPC level was 26.9 g/dl in the control group and 22.5 g/dl in the diabetic patients (p < 0.05). PT and aPTT were similar for the diabetic patients and the controls; however, their corresponding fibrinogen levels were significantly different between the two groups(3.26 +/- 1.14 g/L vs. 4.21 +/- 2.35 g/L, p < 0.05). Our results suggest that platelet hyperfunction in diabetic patients may be implicated in the pathogenesis of diabetic retinopathy.     

糖尿病视网膜病变时血管周细胞的凋亡

周细胞因其自身特点,能够维持血管的稳定性,并能够控制内皮细胞的增殖。周细胞的缺失是糖尿病性视网膜病变(diabetic retinopathy,DR)主要特征之一。当发生DR时,毛细血管周细胞的凋亡途径被激活。人们对周细胞增殖与凋亡机制的研究不断深入,将会从毛细血管周细胞方面找到更多DR治疗的切入点。     

Risk factors for diabetic choroidopathy in patients with diabetic retinopathy

PURPOSE: To identify risk factors for diabetic choroidopathy in patients with type 2 diabetes. METHODS: Forty-five consecutive patients with diabetic retinopathy underwent simultaneous indocyanine green angiography (ICG) and fluorescein angiography using a double detector and confocal scanning laser ophthalmoscopy in both eyes. Choroidal vascular abnormalities were evaluated by comparing the angiographic findings derived from the two methods. We analyzed the association between the presence of abnormal choroidal lesions evident on ICG angiography and several risk factors. RESULTS: Choroidal abnormalities evident on ICG angiography but not on fluorescein angiography included hypofluorescent spots in 72 eyes (80%) of 40 patients (89%), small hyperfluorescent spots in 61 eyes (68%) of 35 patients (78%), and large hyperfluorescent spots in 32 eyes (36%) of 21 patients (47%). The severity of diabetic retinopathy was significantly associated with the presence of hypofluorescent spots ( P=0.002, Cochran-Armitage test) in both eyes and with the small hyperfluorescent spots in the right eyes ( P=0.047, Cochran-Armitage test). Glycosylated hemoglobin levels were significantly associated with the large hyperfluorescent spots in the right eyes ( P=0.003, Fisher's exact probability test), and the treatment regimen was significantly associated with the small hyperfluorescent spots in the left eyes ( P=0.048, chi-square test). CONCLUSION: These data suggest that risk factors influencing the prevalence of diabetic choroidopathy in patients with type 2 diabetes mellitus may include severity of diabetic retinopathy, degree of diabetic control and treatment regimen.     

亚临床期糖尿病视网膜病变的多焦视网膜电流图

多焦视网膜电流图(multifocalelectroretinogram,mERG或mfERG)是一种新兴的眼科检查手段,通过使用特殊m-序列刺激手段短时间内提取局部ERG信号,客观、定量地反映视网膜功能。糖尿病引起的眼部并发症是糖尿病患者致盲的一个主要原因,能够在亚临床期早期诊断糖尿病视网膜疾病(diabeticretinopathy,DR),对于预防和治疗DR有着重要的意义。mERG能够客观地检测DR,应用于研究和临床,评估那些预防和治疗DR方法的效果。     

Factors associated with diabetic macular edema in patients with proliferative diabetic retinopathy

Graefe's Archive for Clinical and Experimental Ophthalmology - To identify factors associated with diabetic macular edema (DME) and to characterize the types of DME present in eyes with...     

Changes in general hemostasis in patients with diabetic retinopathy

The hemostasis system was analyzed in 106 patients with diabetes mellitus, including 86 patients with diabetic retinopathy. Parameters of coagulogram and thromboelastogram as well as platelets aggregation, stimulated by collagen, were examined in all patients. Besides, the fibrinolytic activity of blood plasma as well as the concentration of plasminogen, fibrinogen and of fibrin-degradation products were evaluated. Essential changes were detected, which correlated with an intensity of diabetic changes in the eye fundus, i.e. generalized hypercoagulation caused by a lower activity of the system antithrombin III-heparin, a higher activity of fibrinogen and activation of the fibrinolytic system. The obtained data denote an important role of impaired hemostasis in the pathogenesis of diabetic retinopathy.     

Ocular findings in 123 patients with proliferative diabetic retinopathy

Among 123 patients — 61 men and 62 women — with proliferative diabetic retinopathy, 92% had had diabetes for at least 10 years. In 61%, diabetes had developed before the age of 20 years. Proteinuria was present in 62%, increased serum creatinine levels in 24% and diastolic hypertension in 25%. Of the patients, 20% were blind (visual acuity less than 0.1 in both eyes). Lenticular opacities were seen in 71%, and rubeosis of the iris was present in one third of the eyes. This study was supported by a grant from the Danish Medical Research Council.     

Ocular findings in 123 patients with proliferative diabetic retinopathy

Among 115 diabetic patients with proliferative retinopathy, hemorrhagic glaucoma was found in 22 eyes, and simple glaucoma in four. Otherwise, the intraocular pressure was low in eyes with proliferations, and it was shown that it decreased in parallel with the development of the retinopathy. In some cases, hypotonia was followed by neovascularization in the iris and the chamber angle, and subsequently by hemorrhagic glaucoma.     

Ocular findings in 123 patients with proliferative diabetic retinopathy

The changes in the posterior segment of the eye observed in 123 diabetic patients with proliferative retinopathy are described. In this series, background retinopathy was a frequent occurrence, but it was less pronounced in eyes with severe proliferative retinopathy. All degrees of proliferative retinopathy were encountered; proliferations consisting of naked vessels were observed in 78 eyes, while connective tissue formations were also present in 109 eyes. Posterior vitreous detachment was seen in 105 eyes, and retinal detachment in 52 Vitreous detachment was rare in eyes with vascular proliferations alone, but frequent in eyes with connective tissue formations. Retrovitreal hemorrhages were common, and it is not unlikely that traction by the vitreous on the delicate proliferative vessels is conducive to such hemorrhages.     

Serum SCUBE-1 levels in patients with diabetic retinopathy

International Ophthalmology - Signal peptide-CUB-Epidermal growth factor-like domain-containing protein 1 (SCUBE-1) is a protein expressed on the cell surface of endothelial cells and platelets. We...     

Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy (PDR), an advanced stage of diabetic retinopathy (DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy. METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR (NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I Test, and corneal fluorescein staining. The non-invasive tear film break-up time (NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy. RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls (P< 0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls (P < 0.001). Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover, significant decrease in the corneal epithelial density and morphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients. CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores, and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.