Disease relevance of Diabetic Retinopathy

• Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion [1].
• Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration [2].
• RESULTS: The glycated hemoglobin level at baseline was strongly related to the incidence or progression, or both, of diabetic retinopathy, the incidence of gross proteinuria, and the incidence of loss of tactile sensation or temperature sensitivity in persons with either IDDM or NIDDM [3].
• Angiogenesis, the sprouting of new blood vessels, plays a role in diverse disease states including cancer, diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, psoriasis, atherosclerosis, and restenosis [4].
• Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition [5].

Psychiatry related information on Diabetic Retinopathy

• CONCLUSIONS: Disordered eating behavior is common and persistent in young women with IDDM and is associated with impaired metabolic control and a higher risk of diabetic retinopathy [6].

High impact information on Diabetic Retinopathy

• To determine whether two insulin-like growth factors (IGF I and IGF II) influence the course of diabetic retinopathy, we measured the concentrations of these factors in 80 adult patients with diabetes and in 62 control subjects [7].
• Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy [8].
• In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy [8].
• In humans, vitreal stromal cell-derived factor-1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses [9].
• IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood [10].

Chemical compound and disease context of Diabetic Retinopathy

• These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy [11].
• Fluorescein leakage: First sign of juvenile diabetic retinopathy [12].
• Long-term blood glucose control and diabetic retinopathy [13].
• Angiotensin II, VEGF, and diabetic retinopathy [14].
• Defective homocysteine metabolism as a risk factor for diabetic retinopathy [15].

Biological context of Diabetic Retinopathy

• Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability [16].
• These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that aminoguanidine may have future therapeutic use in this disorder [17].
• High levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD) [18].
• An (A-C)n dinucleotide repeat polymorphic marker at the 5' end of the aldose reductase gene is associated with early-onset diabetic retinopathy in NIDDM patients [19].
• Protein kinase C beta2-dependent phosphorylation of core 2 GlcNAc-T promotes leukocyte-endothelial cell adhesion: a mechanism underlying capillary occlusion in diabetic retinopathy [20].

Anatomical context of Diabetic Retinopathy

• Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique specificity for endothelial cells and a key mediator of aberrant endothelial cell proliferation and vascular permeability in a variety of human pathological situations, such as tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, or psoriasis [21].
• These data identify the causal role of leukocytes in the pathogenesis of diabetic retinopathy and establish the potential utility of ICAM-1 inhibition as a therapeutic strategy for the prevention of diabetic retinopathy [5].
• Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy [22].
• There is also evidence linking AR activity with retinal capillary basement membrane thickening in galactosemic rats, suggesting a possible role in diabetic retinopathy [23].
• Activity of the glycosylating enzyme, core 2 GlcNAc (beta1,6) transferase, is higher in polymorphonuclear leukocytes from diabetic patients compared with age-matched control subjects: relevance to capillary occlusion in diabetic retinopathy [24].

Gene context of Diabetic Retinopathy

• Vitreous from patients with proliferative diabetic retinopathy but without rubeosis (n = 16) contained 2.5- and 2.2-fold elevated levels of IGF-I and of IGFBP-2 (P < 0.05), while IGF-II and IGFBP-3 were increased 1.4- and 1.6-fold, which was not significant [25].
• OBJECTIVE: To evaluate vitreous levels of IGF-I and its binding proteins IGFBP-1 and IGFBP-3 in patients with proliferative diabetic retinopathy (PDR) [26].
• Vitreous levels of IGF-I, IGF binding protein 1, and IGF binding protein 3 in proliferative diabetic retinopathy: a case-control study [26].
• The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of prepro-NPY is associated with increased blood lipid levels, accelerated atherosclerosis, and diabetic retinopathy [27].
• No association between the MTHFR gene polymorphism and diabetic retinopathy in type 2 diabetic patients without overt nephropathy [28].
• Our findings suggest that this IGF-I gene polymorphism is associated with an increased risk of diabetic retinopathy [29].

Analytical, diagnostic and therapeutic context of Diabetic Retinopathy

• To investigate this relationship and potential associations between other polymorphic genes and proliferative retinopathy, a sample (n = 428) of participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy was selected for typing for HLA-A, -B, -C, and -DR and a panel of other polymorphic genes [30].
• Determinants of proliferative diabetic retinopathy (PDR) that occur during the 2nd decade of insulin-dependent diabetes mellitus (IDDM) (early-onset PDR) were investigated in a nested case-control study [31].
• In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy [32].
• The alterations we observed suggest that local release of angiostatin and down-regulation of vascular endothelial growth factor mediate the therapeutic effects of retinal photocoagulation in proliferative diabetic retinopathy [33].
• Pharmacological inhibition of in vivo AGE formation by aminoguanidine prevents or ameliorates diabetic retinopathy, nephropathy, and neuropathy in animal models [34].

References