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Biomedical subjects

H P Hammes

Publications and source records attributed to H P Hammes.

At least 19 recordsLinked to original sources
PubMed2005

Adult vascular progenitor cells and tissue regeneration in metabolic syndrome.

Adult vascular progenitor cells (for example endothelial progenitor cells, EPC) have been studied for their contribution to vascular repair and angiogenesis. These cells can differentiate from bone marrow cells as well as circulating cells carrying hematopoetic stem cell markers. In vivo, they take part in vasculogenesis in different animal models of limb ischemia, myocardial infarction and wound healing. In metabolic disease, the outgrowth and function of EPC in vitro is defective and numbers of EPC correlate with classical risk factors of cardiovascular disease suggesting a role of EPC in the development of vascular complications. Pilot studies for the treatment of myocardial infarction and limb ischemia with autologous bone marrow showed a distinct therapeutic benefit that is presumably mediated by vasculogenesis in damaged tissues. However, little is known about the nature of EPC and their capability to differentiate into functional cells for tissue regeneration. In this article, we review and discuss the hitherto identified physiological function of EPC, the mechanisms leading to dysfunction of these cells and potential therapeutic applications in patients with metabolic syndrome or diabetes mellitus and vascular complications.

Adult↗
PubMed2005

Early loss of arteriolar smooth muscle cells: more than just a pericyte loss in diabetic retinopathy.

Incipient diabetic retinopathy is characterized by increased capillary permeability and progressive capillary occlusion. The earliest structural change is the loss of pericytes (PC) from the retinal capillaries. With the availability of the XLacZ mouse, which expresses the LacZ reporter in a PC/vascular smooth muscle cell (vSMC) specific fashion, we quantitatively assessed the temporal dynamics of smooth muscle cells in arterioles under hyperglycemic conditions. We induced stable hyperglycemia in XLacZ mice. After 4, 8, and 12 weeks of diabetes retinae were isolated and beta-galactosidase/lectin stained. The numbers of smooth muscle cells were counted in retinal whole mounts, and diameters of retinal radial and branching arterioles and venules were analyzed at different distances apart from the center of the retina. After eight weeks of diabetes, the numbers of vSMCs were significantly reduced in radial arterioles 1000 microm distant from the optic disc. At proximal sites of branching arterioles (400 microm distant from the center), and at distal sites (1000 microm), vSMC were significantly reduced already after 4 weeks (to a maximum of 31 %). These changes were not associated with any measurable variation in vessel diameters. These data indicate quantitatively that hyperglycemia not only causes pericyte loss, but also loss of vSMCs in the retinal vasculature. Our data suggest that arteriolar vSMC in the eye underlie similar regulations which induce early pericyte loss in the diabetic retina.

Animals↗
PubMed2003

Angiogenic capacity of endothelial cells in islets of Langerhans.

Transplantation of pancreatic islets reconstitutes glucose homeostasis in diabetes mellitus. Before transplantation, islets are disrupted from the surrounding blood vessels by the isolation procedure, with the grafted tissue being subject to ischemic damage. The survival of transplanted islets is assumed to depend on effective revascularization. Perfusion studies suggest that newly formed microvessels supplying the graft with nutrients are exclusively rebuilt by the host. It is generally not known whether isolated islets contain endothelial cells (EC), which potentially participate in the revascularization process. Therefore, we tried to detect immature EC in isolated islets by transformation with polyoma middle T antigen. Endothelioma cells were generated, implicating the presence of de-differentiated EC within isolated islets. When embedded in a fibrin gel, the islets developed cellular cords consisting of EC, whereas FGF-2 and VEGF stimulated the formation of cord-like structures. Furthermore, we studied the presence of donor EC in islet grafts by using transgenic mice with an EC lineage-specific promotor-LacZ reporter construct (Tie-2LacZ). Following islet transplantation, Tie-2LacZ-positive EC of both donor and recipient were identified in the vicinity of or within the graft up to 3 wk after transplantation. In conclusion, EC and/or their progenitors with angiogenic capacity reside within isolated islets of different species, and their proliferative potential can be stimulated by various inducers. These graft-related endothelia persist after islet transplantation and are integrated within newly formed microvessels.

Animals↗
PubMed2001

Topical application of integrin antagonists inhibits proliferative retinopathy.

The expression of alphav-integrins is highly selective for angiogenic endothelial cells; ligation inhibition by cyclic RGD peptides prevents pathological neovascularization in tumor or retinopathy models to a large extent. We have previously demonstrated that proliferative retinopathy in a mouse model of retinopathy of prematurity (ROP model) can be reduced by more than 70%. To minimize systemic side effects and unwanted interference with responsive angiogenesis, we investigated topical application of cyclic RGD-peptides. In preliminary experiments, we could exclude any inhibiting effects of the carrier solution containing EDTA, Na2S, mannitol, hydroxyethyl starch, and benzalconium chloride on the inhibitory effect of cyclic RGD peptides. Retinal presence of small molecular-mass integrin antagonists after topical application was confirmed using fluorescein-labeled cyclic RGD peptide. Topical application of the peptide to the eye inhibited proliferative retinopathy in a dose-dependent fashion with a maximum of almost 50%. These results suggest that small molecular-mass peptide antagonists of alphav-type integrins are efficient in inhibiting proliferative retinopathy by topical application.

Adhesiveness↗
PubMed2001

Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats.

In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

Animals↗
PubMed2001

Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease.

Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P = 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR.

Aged↗
PubMed2000

Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions.

Proteolytic cleavage of single-chain high molecular weight kininogen (HK) by kallikrein releases the short-lived vasodilator bradykinin and leaves behind 2-chain high molecular weight kininogen (HKa) that has been previously reported to exert antiadhesive properties as well as to bind to the urokinase receptor (uPAR) on endothelial cells. In this study we defined the molecular mechanisms for the antiadhesive effects of HKa related to disruption of integrin- and uPAR-mediated cellular interactions. Vitronectin (VN) but not fibrinogen or fibronectin-dependent alphavbeta(3) integrin-mediated adhesion of endothelial cells was blocked by HKa or its isolated domain 5. In a purified system, HKa but not HK competed for the interaction of VN with alphavbeta(3) integrin, because HKa and the isolated domain 5 but not HK bound to both multimeric and native VN in a Zn(2+)-dependent manner. The interaction between HKa or domain 5 with VN was prevented by heparin, plasminogen activator inhibitor-1, and a recombinant glutathione-S-transferase (GST)-fusion peptide GST-VN (1-77) consisting of the amino terminal portion of VN (amino acids 1-77), but not by a cyclic arginyl-glycyl-aspartyl peptide, indicating that HKa interacts with the amino terminal portion of VN ("somatomedin B region"). Furthermore, we have confirmed that HKa but not HK bound to uPAR and to the truncated 2-domain form of uPAR lacking domain 1 in a Zn(2+)-dependent manner. Through these interactions, HKa or its recombinant His-Gly-Lys-rich domain 5 completely inhibited the uPAR-dependent adhesion of myelomonocytic U937 cells and uPAR-transfected BAF-3 cells to VN and thereby promoted cell detachment. By immunogold electron microscopy, both VN and HK/HKa were found to be colocalized in sections from human atherosclerotic coronary artery, indicating that the described interactions are likely to take place in vivo. Taken together, HK and HKa inhibit different VN-responsive adhesion receptor systems and may thereby influence endothelial cell- or leukocyte-related interactions in the vasculature, particularly under inflammatory conditions. (Blood. 2000;96:514-522)

Arteriosclerosis↗
PubMed2000

Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.

Diabetic hyperglycaemia causes a variety of pathological changes in small vessels, arteries and peripheral nerves. Vascular endothelial cells are an important target of hyperglycaemic damage, but the mechanisms underlying this damage are not fully understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase C isoforms; increased formation of glucose-derived advanced glycation end-products; and increased glucose flux through the aldose reductase pathway. The relevance of each of these pathways is supported by animal studies in which pathway-specific inhibitors prevent various hyperglycaemia-induced abnormalities. Hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells. Here we show that this increase in reactive oxygen species is prevented by an inhibitor of electron transport chain complex II, by an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase. Normalizing levels of mitochondrial reactive oxygen species with each of these agents prevents glucose-induced activation of protein kinase C, formation of advanced glycation end-products, sorbitol accumulation and NFkappaB activation.

Animals↗
PubMed2000

Release of the angiogenesis inhibitor angiostatin in patients with proliferative diabetic retinopathy: association with retinal photocoagulation.

AIMS/HYPOTHESIS: Proliferative diabetic retinopathy is a major debilitating disease causing most cases of blindness in humans in the Western world. Photocoagulation is the established therapy of proliferative diabetic retinopathy, although the molecular mechanisms of its effects are still not known. Recently angiostatin has been characterized as a potent inhibitor of neovascularization. Apart from a possible down-regulation of angiogenic cytokines, release of angiostatin could initiate the anti-angiogenic effects of retinal photocoagulation. METHODS: We investigated the regulation of angiostatin and the angiogenic cytokines vascular endothelial growth factor and basic fibroblast growth factor in vivo by comparing vitreal concentrations of 18 control patients and 34 patients with proliferative diabetic retinopathy with and without previous photocoagulation. Concentrations of basic fibroblast growth factor and angiostatin were additionally measured in serum, while vascular endothelial growth factor is known to be regulated locally in the eye. Cytokines were measured by immunological methods. RESULTS: Angiostatin could be detected in 2 out of 18 control patients and in 25 out of 34 diabetic patients (p < 0.00001). Most importantly, production of angiostatin in human vitreous correlated significantly with previous retinal photocoagulation (p < 0.0001) in patients with proliferative diabetic retinopathy. Only two patients (one control and one diabetic) had detectable serum concentrations of angiostatin. Additionally patients with proliferative diabetic retinopathy and with previous photocoagulation had significantly lower concentrations of vascular endothelial growth factor (0.9 +/- 0.1 ng/ml; p < 0.0001) than diabetic patients without previous photocoagulation (4.0 +/- 0.8 ng/ml). The investigation of vitreal and serum basic fibroblast growth factor concentrations yielded no significant differences between the groups. CONCLUSION/INTERPRETATION: Angiostatin is not a regularly expressed angiogenesis inhibitor in human vitreous. 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.

Aged↗
PubMed2000

Ocular pulse amplitude in diabetes mellitus.

BACKGROUND: The influence of diabetes mellitus on ocular pulse amplitude (OPA), an indirect measure of choroidal perfusion, is unclear. METHODS: OPA, using the Langham ocular blood flow (OBF) system, applanation intraocular pressure (IOP), systemic blood pressure (BP), heart rate, and haemoglobin (Hb) A(1c) were measured in patients with insulin dependent diabetes mellitus (IDDM) with no (DR-0, n = 22) non-proliferative (DR-1, n = 24), and proliferative (DR-2, n = 18) diabetic retinopathy. RESULTS: Neither local (OPA, IOP) nor systemic perfusion parameters (BPs, HR) nor HbA(1c) were significantly altered in DR-0, DR-1, or DR-2 IDDM patients. CONCLUSION: Choroidal circulation remains unaffected as diabetic retinopathy advances.

Adult↗
PubMed1999

Diabetic retinopathy risk correlates with intracellular concentrations of the glycoxidation product Nepsilon-(carboxymethyl) lysine independently of glycohaemoglobin concentrations.

AIMS/HYPOTHESIS: We investigated whether either the amount of diabetes-induced intracellular oxidative stress or the concentration of hyperglycaemia-induced advanced glycation endproducts is associated with the risk of diabetic retinopathy. METHODS: We measured concentrations of the glycoxidation product Nepsilon-(carboxymethyl)lysine and two non-oxidation-dependent advanced glycation end-products (methylglyoxal-derived and 3-deoxyglucosone-derived) in CD45RA+ T-cells from 21 Type I (insulin-dependent) diabetic patients with and without diabetic retinopathy and from age-matched nondiabetic control subjects. RESULTS: Intracellular concentrations of both oxidation-dependent Nepsilon-(carboxymethyl)lysine and oxidation-independent advanced glycation endproducts were increased in memory T-cells from diabetic patients. Nepsilon-(carboxymethyl)lysine: diabetic median-24176 arbitrary units/mg protein (95% confidence interval 18690-34099 arbitrary units/mg protein); nondiabetic-9088 arbitrary units/mg protein (confidence interval 6994-10696 arbitrary units/mg protein; p < 0.0001). Methylglyoxal-derived advanced glycation end products: diabetic-5430 arbitrary units/ mg protein (confidence interval 3458-13610); nondiabetic-271 arbitrary units/mg protein (confidence interval 61-760 arbitrary units/mg protein; p< 0.0001). 3-Deoxyglucosone-derived advanced glycation end products: diabetic-8070 arbitrary units/mg protein (confidence interval 7049-16551 arbitrary units/mg protein); nondiabetic-1479 arbitrary units/ mg protein (confidence interval 1169-3170; p< 0.0001). Only Nepsilon-(carboxymethyl)lysine concentrations, however, inversely correlated with the duration of retinopathy-free diabetes (r = -0.51; p < 0.02). Diabetes-dependent Nepsilon-(carboxymethyl)lysine accumulation did not correlate with age, diabetes duration, or averaged glycohaemoglobin concentrations. In vitro experiments wih menadione and lymphocytes confirmed that Nepsilon-(carboxymethyl)lysine concentrations reflect intracellular oxidative stress. CONCLUSION/INTERPRETATION: Monitoring intracellular concentrations of increased oxidative stress in long-lived CD45RA+ lymphocytes by markers such as Nepsilon-(carboxymethyl)lysine possibly identifies a subgroup of patients at high risk for microvascular complications.

Adult↗
PubMed1999

Differential accumulation of advanced glycation end products in the course of diabetic retinopathy.

AIMS/HYPOTHESIS: Glycated proteins, formed by reaction of glucose and protein, react further yielding numerous, mostly undefined advanced glycation end products (AGE). The recently characterized imidazolone-type AGE (AG-1) is non-oxidatively formed involving 3-deoxyglucosone whereas some AGEs, particularly N(epsilon)-(carboxymethyl)lysine (CML), are formed only in the presence of oxygen. METHODS: To study the possible contribution of oxidative and non-oxidative AGE formation in the development of diabetic retinopathy antibodies directed against CML-type and imidazolone-type AGEs were characterized by dot blot analysis and used to localize these well-characterized epitops in the retinas from diabetic rats (early course) and from human Type I (insulin-dependent) diabetes mellitus with laser-treated proliferative diabetic retinopathy (late course). RESULTS: In non-diabetic rats CML was moderately positive in neuroglial and vascular structures of non-diabetic rat retinas and increased strongly in diabetic retinas. Anti-imidiazolone antibody staining was strongly positive only in diabetic capillaries. Advanced human diabetic retinopathy showed strong CML-immunolabelling of the entire retina whereas control samples showed moderate staining of neuroglial structures only with the polyclonal CML-antibody. Anti-imidiazolone antibody staining was faint in the inner retina of control sections but were strong throughout the entire diabetic retina. Immunolabelling for the AGE-receptor was congruent with a marker of Müller cells. CONCLUSION/INTERPRETATION: Our data indicate that the oxidatively formed CML is present in non-diabetic retinas as a regular constituent but increases in diabetes both in neuroglial and vascular components. Imidazolone-type AGE are restricted to microvessels and spread during later stages over the entire retina, co-localizing with the expression of AGE-receptor.

Animals↗
PubMed1999

N(epsilon)(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration.

PURPOSE: To investigate whether glycoxidation products and the receptor for advanced glycation end products (RAGE) are present and colocalize in subfoveal membranes of patients with age-related macular degeneration (ARMD). METHODS: Surgically removed subfoveal fibrovascular membranes from 12 patients, 11 related to ARMD and 1 to an idiopathic membrane, were analyzed for the presence of the glycoxidation product N(epsilon)-(carboxymethyl)lysin (CML), one of the receptors for advanced glycation end products, RAGE, and the activation of NFkB, using immunohistochemistry. RESULTS: CML-like immunoreactivity was found in all ARMD specimens examined adjacent or colocalized with RAGE, but not in the idiopathic membrane. RAGE immunoreactive material was found in CD68-positive cells and in the fibrous matrix. CD68-positive cells and surrounding areas stained for p50, the activated form of NFkB. CONCLUSIONS: These results indicate that glycoxidation products are present in subretinal membranes of patients with ARMD. The concomitant expression of RAGE in these membranes and the finding of activated NFkB is suggestive of an implication of glycoxidation product formation in the pathogenesis of the disease.

Adolescent↗
PubMed1998

The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster.

To assess the relationship between glucose and advanced glycation end products (AGE) and the relationship between AGE and retinal changes in vivo, we studied the time course of retinopathy over 12 months in trypsin digest preparations and measured glycaemia and retinal AGE in spontaneous diabetic hamsters of mild (MD) and severe (SD) phenotypes. Blood glucose levels were elevated in MD (9.44+/-0.76 mmol/l) and in SD (3 months: 24.3+/-1.4 mmol/l; 12 months: 31.7+/-0.8 mmol/l) over non-diabetic controls (NC: 7.15+/-0.25 mmol/l; p < 0.05 or less vs MD; p < 0.001 vs SD). Similar relations were found for HbA1. Retinal AGE in mild diabetes was 405+/-11.3 arbitrary units (AU) (NC 245+/-7.7; p < 0.01) after 3 months and remained unchanged. A non-linear increase of AGE over time was found in severe hyperglycaemic hamsters (466+/-21 AU after 3 months and 758+/-21 AU after 12 months; p < 0.001 vs MD). Pericyte loss in mild diabetes progressed from -26% after 3 months to 41% after 12 months (p < 0.001 vs NC). Whereas the initial pericyte loss in severely diabetic hamsters was identical to the mildly diabetic group, a higher degree of pericyte loss occurred after 12 months (-57%; p < 0.05 vs MD). Endothelial cell numbers remained unaffected by mild hyperglycaemia, but significantly increased over time in severe diabetes reaching 31.7% above controls after 12 months (p < 0.001 vs NC and MD). Microaneurysms were absent in all retinae examined. Acellular capillary segments were increased in mild diabetes (3.83+/-0.31 per mm2 of retinal area) and severe diabetes (7.83+/-0.73) over controls (1.0+/-0.23). These data suggest that a threshold of glycaemia might exist above which AGE removal systems become saturated. Pericyte loss and acellular capillary formation are associated with mild increases in blood glucose and AGE levels while endothelial cell proliferation requires higher glucose and AGE levels.

Animals↗
PubMed1998

Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat.

Vascular endothelial growth factor (VEGF) is a major contributor to retinal neovascularization. The possible participation of VEGF and its high-affinity tyrosine kinase receptors, flk-1 and flt-1, in early background diabetic retinopathy was studied in the streptozotocin-induced diabetic rat model of experimental retinopathy using in situ hybridization, blotting techniques, and immunohistochemistry. Diabetic retinopathy was assessed by quantitative morphometry of retinal digest preparations. The number of acellular capillaries increased 2.7-fold in diabetic animals with diabetes' duration of 6 months compared with nondiabetic controls. VEGF expression was not detectable by in situ hybridization in nondiabetic rats but was highly increased in the ganglion cell layer and in the inner and outer nuclear layers of retinas from diabetic animals. VEGF protein was extractable only from diabetic retinas, and a strong immunolabeling was detected in vascular and perivascular structures. Increased flk-1 and flt-1 mRNA levels were also found in the ganglion cell and both nuclear layers of diabetic samples only. Dot blot and Western blot analyses confirmed the increase in flk-1 mRNA and protein in diabetic retinas. Also, flk-1 immunoreactivity was associated with vascular and nonvascular structures of the inner retinas from diabetic animals. These data obtained from a rodent model in which retinal neovascularization does not occur support the concept that the VEGF/VEGF receptor system is upregulated in early diabetic retinopathy.

Animals↗
PubMed1997

Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine.

In order to study the contribution of oxidant stress to the pathogenesis of experimental diabetic retinopathy, male streptozotocin diabetic Lewis rats were treated with the antioxidant and lipid-lowering compound nicanartine (80 mg/kg; n = 8, blood glucose level 16.7 +/- 3.9 mmol/l; HbA1 11.8 +/- 1.6%) by oral supplementation for 6 months and compared with untreated diabetic (n = 6; blood glucose 18.1 +/- 1.4 mmol/l; HbA1 11.5 +/- 1.5%) and untreated, non-diabetic rats (n = 8; blood glucose 4.0 +/- 0.6 mmol/l; HbA1 4.8 +/- 0.9%). Diabetic retinopathy was evaluated by computer-assisted quantitative morphometry including measurement of autofluorescent advanced glycated end-products and immunohistochemistry for heme oxygenase I. Antioxidant treatment did not inhibit the 3.1-fold increase of retinal advanced glycation end products, while the expression of heme oxygenase I in both vascular and glial structures was markedly reduced. Chronic hyperglycaemia led to a 37.3% increase in endothelial cells (p < 0.001 vs normal controls) and a 26.6% reduction in pericyte numbers (p < 0.001 vs controls). Both abnormalities were significantly ameliorated by nicanartine (p < 0.001 vs diabetic controls). No effect was observed on the formation of acellular capillaries or microaneurysms. These data indicate that antioxidant therapy with nicanartine is of limited benefit in diabetic retinopathy, at least in the rodent model of streptozotocin-induced diabetes.

Animals↗
PubMed1997

Integrin chatter and vascular function in diabetic retinopathy.

The interplay between adhesion receptors and proteolytic cascades is crucial for cell proliferation and migration in the (patho-)physiology of vascular function. Disregulated angiogenesis in diabetic retinopathy appears to be associated with the appearance of advanced glycation end products that disturb interactions between capillary cells and extracellular matrix. Vitronectin receptor-type integrins are expressed on angiogenic endothelial cells and contribute to unwanted vascular sprouting in the retinal tissue. In a hypoxia-induced retinal neovascularization model, intervention with low molecular weight integrin antagonist resulted in significant reduction of unwanted angiogenesis indicating that this angiostatic therapy appears to be promising also for late complications in diabetes.

Diabetic Retinopathy↗