Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesis in vivo in humans. The current understanding of molecular biology involved in angiogenesis has already led to the identification of a number of potential therapeutic targets, some of them being highly effective angiostatic molecules. Most experimental approaches currently favour or even require the systemic administration of the investigated substances (somatostatin analogues, PKC-inhibitors). However, the systemic administration of bioactive substances always risks significant systemic adverse effects. Due to the morphological characteristics of the eye, local therapies including intraocular injection or even local gene transfer might be feasible. They might provide a valuable opportunity of targeted and sustained delivery of therapeutic proteins to the retina. This review aims to outline the current understanding of the pathogenesis of proliferative diabetic retinopathy and will focus on some as yet experimental, but potentially effective new therapeutic possibilities of this disease.
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PMID:Novel approaches in the treatment of angiogenic eye disease. 1602 67

Proliferative diabetic retinopathy is the main cause of vision loss in young and middle-aged adults. There is no accepted pharmaceutical therapy for this disease, although analogs of the naturally occurring growth hormone inhibitor, somatostatin, have been considered leading candidates for developing such therapies. This review examines the history of somatostatin analogs, especially octreotide, in the treatment of ocular complications of diabetes mellitus. The historical observations that indicated a role for somatostatin in retinopathy are discussed from an endocrinology perspective. The molecular mechanisms by which somatostatin may exert its anti-angiogenic effects, both indirect (through antagonism of the growth hormone axis) and direct (through direct antiproliferative and apoptotic effects on endothelial cells mediated by specific receptor subtypes) are described. Animal models that were used to demonstrate an anti-angiogenic effect of octreotide are detailed, as are the results of numerous clinical trials that used octreotide and other somatostatin analogs to treat diabetic retinopathy. The mixed results of these clinical results are examined along with possible explanations as to why these analogs both have and have not shown efficacy in limited clinical settings. Even with these mixed results, somatostatin analogs remain the only therapeutic alternative to patients with proliferative diabetic retinopathy who have failed to respond to panretinal photocoagulation.
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PMID:The potential role of octreotide in the treatment of diabetic retinopathy. 1605 37

Traditional management strategies for retinal neovascularisation accompanying proliferative diabetic retinopathy include photocoagulation laser therapy. The development of preventative pharmacological treatments aimed at replacing or delaying this acute intervention has been an active research area and somatostatin analogues have shown promise in reducing the progression of retinal vascular pathologies. This review summarises the present knowledge on the molecular and cellular mechanisms of neovascularisation, and the rationale for the therapeutic use of somatostatin analogues as well as the results of two key recent clinical trials using octreotide. The potential use of octreotide and other somatostatin analogues in reducing the risk of severe visual impairment in proliferative diabetic retinopathy is discussed and pharmacological treatment regimens are proposed as an additional strategy or a less invasive alternative to laser therapy.
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PMID:Medical treatment of diabetic retinopathy with somatostatin analogues. 1715 55

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are implicated in the aberrant cell growth and pathological neovascularization that characterises proliferative diabetic retinopathy. While serum levels of IGF-I are reported to be either high or low in diabetic patients, there is evidence that local tissue levels of IGF-I may be more relevant to diabetic retinal pathology. IGF-I and IGF binding proteins (IGFBP) are expressed throughout the retina in vascular, neuronal and glial cells, and are altered in response to hyperglycaemia and hypoxia. Further support for a pathological role for local IGF-I comes from studies showing IGF-I to be increased in the vitreal fluids of patients with proliferative diabetic retinopathy. IGF-I may exert its cell growth promoting properties by stimulating a number of pathways including protein-kinase B (Akt), nuclear factor kB (NF-kappaB)/AP-1 and hypoxic-inducible factor-1alpha (HIF-1alpha). In addition, other growth factors may participate in IGF-I induced cell growth including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF). The importance of the GH/IGF system in diabetic retinopathy and retinal neovascularization has been highlighted by the use of agents that inhibit the system. GH receptor antagonists, GH receptor antisense oligonucleotides, somatostatin analogues and receptor neutralising antibodies to IGF-I reduce hypoxic-induced retinal neovascularization. These approaches may also prove to have benefits for improving vascular patency and vision in patients with diabetic retinopathy.
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PMID:The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. 1716 53

The diabetes epidemic continues unabated, leading to an increasing number of acute and chronic complications, including sight-threatening proliferative diabetic retinopathy. Currently, there is no accepted pharmaceutical therapy for diabetic retinopathy besides nearnormal glycemia, treatment of hypertension, and dyslipidemia. For an effective treatment of retinopathy, one would recommend a concept leading to the downregulation of endogenous angiogenic stimulators and the upregulation of endogenous angiogenic inhibitors, resulting in a restoration of the balance in angiogenic control. The naturally occurring growth hormone inhibitor, somatostatin, has been suggested as candidate for developing novel therapies. Somatostatin may exert its antiangiogenic effects, both through antagonism of the growth hormone axis and through direct antiproliferative and apoptotic effects on endothelial cells. Therefore, the use of long-acting somatostatin analogues will lead to an upregulation of antiangiogenic signaling. Use of long-acting somatostatin analogues in diabetic retinopathy would be an important extension of the initial concept that somatostatin is a regulator of growth hormone secretion only. Currently available analogues have already allowed to modulate the expression of diabetic retinopathy at various disease stages. Somatostatin analogues remain the only nondestructive therapeutic alternative to patients with proliferative diabetic retinopathy who have failed to respond to panretinal photocoagulation.
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PMID:Use of long-acting somatostatin analogue treatment in diabetic retinopathy. 1724 82

Proliferative diabetic retinopathy (PDR) demands both more effective and less expensive biologically based treatments. Our understanding of the pathophysiology of the disease is increasing as new biochemical pathways are identified. Most reports emphasize proangiogenic stimuli, with the natural inhibitory elements receiving little attention. There are two therapeutic strategies for blocking retinal angiogenesis in PDR: systemic drug administration (protein kinase C inhibitors and somatostatin analogs) or local therapies (anti-vascular endothelial growth factor strategies, anti-inflammatory agents, gene therapy and stem cell therapy). This review mainly focuses on the role of local therapies, especially intravitreous delivery, in the management of PDR. The potential for adverse effect are also discussed. The availability of these new strategies or the combination of them will not only be beneficial in treating PDR but may also result in a shift towards treating earlier stages of diabetic retinopathy, thus easing the burden of this devastating disease.
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PMID:Strategies for blocking angiogenesis in diabetic retinopathy: from basic science to clinical practice. 1768 70

Diabetic retinopathy continues to be the leading cause of legal blindness among working-age individuals. The earliest histological features of diabetic retinopathy include neuroretinal damage, capillary basement membrane thickening, loss of pericytes and loss of endothelial cells. At advanced stages, neovascularization, the hallmark of proliferative diabetic retinopathy (PDR) occurs, and blindness can result from relentless abnormal fibrovascular proliferation with subsequent bleeding and retinal detachment. Macular oedema is another retinal complication of diabetes that is responsible for a major part of vision loss, particularly in type 2 diabetes. The breakdown of the blood retinal barrier and the consequent vascular leakage and thickening of retina are the main events involved in its pathogenesis. Although a tight control of both blood glucose levels and hypertension are essential to prevent or arrest progression of the disease, the recommended goals are difficult to achieve in many patients. Laser photocoagulation treatment soon after the onset of PDR significantly reduces the incidence of severe vision loss. However, the optimal timing for laser treatment is frequently passed and, in addition, it is not uniformly successful in halting visual decline. For all these reasons, new pharmacological treatments based on the understanding of the pathophysiological mechanisms of diabetic retinopathy have been developed in recent years. There is mounting evidence to suggest that angiogenic factors play a crucial role in PDR development, vascular endothelial growth factor (VEGF) being the most relevant. Other growth factors or cytokines such as insulin-like growth factor I (IGF-1), hepatocyte growth factor (HGF), basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), pro-inflammatory cytokines and angiopoetins, are also involved in the pathogenesis of PDR. However, the intraocular synthesis of angiogenic factors is counterbalanced by the synthesis of antiangiogenic factors. Therefore, the balance between the angiogenic and antiangiogenic factors rather than angiogenic factors themselves will be crucial in determining the progression of PDR. The main antiangiogenic factor is the pigment epithelium derived factor (PEDF) but the transforming growth factor beta (TGF-beta), thrombospondin (TSP) and somatostatin are also among the intraocullary synthesized antiangiogenic factors.
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PMID:Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. 1822 Jun 19

Somatostatin, a polypeptide hormone of 14 or 28 aminoacids, is produced by neuroendocrine, inflammatory and immune cells. It has multiple inhibitory functions on the secretion of various hormones and growth factors and modulates several cellular functions. Somatostatin analogues provide an elegant pharmacological principal to modify the high-risk form of proliferative diabetic retinopathy. Pilot investigations have provided evidence that octreotide can very effectively suppress new bleeding and stop visual loss in patients who have failed conventional photocoagulation therapy. In this cohort, octreotide was found to be a safe treatment modality. The same applies also for thyroid eye disease, in which some non-randomized, as well as randomized studies have shown a beneficial effect. More potent analogues, like SOM230, which are not yet in the market, can be proved to have a better therapeutic outcome in such patients and may be considered a safe treatment modality to stop the progression from pre-proliferative to proliferative diabetic retinopathy. This is also true for adolescent patients with thyroid eye disease, as well as for adults who also suffer from diabetes mellitus.
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PMID:The efficacy of somatostatin analogues in the treatment of diabetic retinopathy and thyroid eye disease. 1966 74


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