Article

Diabetische Makulopathie

Der Ophthalmologe (Impact Factor: 0.5). 08/2010; 107(8):773-788. DOI: 10.1007/s00347-010-2202-z

ABSTRACT

Trotz medikamentöser Fortschritte und teurer Präventionsprogramme steigt die Prävalenz der diabetischen Retinopathie, einer
der häufigsten Erblindungsursachen in Deutschland, aufgrund des demografischen Wandels weiter an. Nach wissenschaftlichem
Stand ist die „focal/grid“-Laserkoagulation, in Kombination mit der intravitrealen operativen Medikamentenapplikation (IVOM)
von VEGF-Inhibitoren (VEGF: „vascular endothelial growth factor“), zurzeit die wirksamste Therapie des klinisch signifikanten
Makulaödems mit Foveabeteiligung. Vitreomakuläre Interface-Anomalien erfordern den Einsatz der modernen Netzhautchirurgie.
Für die ischämische Makulopathie gibt es keine effektive Behandlung. Die zeitgemäße Einstellung des Blutzuckerspiegels und
die optimale Kontrolle relevanter Risikofaktoren haben in der interdisziplinären Abstimmung einen festen Stellenwert. Innovative
Entwicklungen in der pharmakologischen Therapie eröffnen eine optimistische Perspektive auf mögliche Funktionsverbesserungen,
die die Lebensqualität der Diabetespatienten steigern werden.

Due to demographic change the incidence of diabetic retinopathy has risen in spite of new facilities and prevention campaigns
and is still one of the leading causes of blindness in Germany. The combination of focal/grid laser photocoagulation and an
intravitreal anti-VEGF (vascular endothelial growth factor) regimen is the first line approach for clinically significant
macular edema with foveal involvement and is evidence-based. Vitreomacular interface abnormalities can be effectively treated
by modern vitreomacular surgery. Unfortunately, no proven treatment modality can be provided for ischemic maculopathy. The
management of systemic risks factors, such as hyperglycemia and arterial hypertension, remains a task of great importance
despite all modifications and increase of knowledge during recent years. Innovative developments in the field of intravitreal
pharmacotherapy have opened up new vistas. There are good prospects that modern ophthalmology will not be limited to preserving
visual function but to allow improvements and consequently enhance health-related quality of life for diabetic patients.

SchlüsselwörterDiabetische Makulopathie-Makulaödem-Laserkoagulation-Anti-VEGF-Therapie-HbA1c (Glykohämoglobin)
KeywordsDiabetic retinopathy-Macula edema-Laser photocoagulation-Anti-VEGF therapy-HbA1c (glycohemoglobin)

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    ABSTRACT: Retinopathy has been observed in around quarter of diabetic patients. Diabetic retinopathy can result in poor vision and even blindness since high glucose has been evidenced to weaken retinal capillary leading to leakage of blood into the surrounding space. In the present study, a proteomics-based approach has been applied to analyze a model retinal pigmented epithelium cell line, ARPE-19, grown in mannitol-balanced 5.5mM, 25mM and 100mM D-glucose culture media and used as a model for hyperglycemia secretomic analysis. Totally, 55 differentially secreted proteins have been firmly identified representing 46 unique gene products. These secreted proteins mainly function in cytoskeleton-associated adhesion/junction (such as galectin-3-binding protein) and transport (multidrug resistance-associated protein 1). Additionally, the identified secreted markers including asialoglycoprotein receptor 1, lysophosphatidic acid receptor 3, moesin, MPP2, haptoglobin and cathepsin D were further validated in plasma samples coming from type 2 diabetic patients with retinopathy and healthy donors. In summary, we report a comprehensive retinal cell-based proteomic approach for the identification of potential secreted retinal markers-induced in high glucose conditions. Some of these identified secreted proteins have been validated in diabetic retinopathy plasma demonstrating the potentially utilizing of these markers in screening and treating diabetic retinopathy.
    No preview · Article · Jul 2012 · Journal of proteomics
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    ABSTRACT: Diabetic retinopathy can cause poor vision and blindness. Previous research has shown that high blood glucose weakens retinal capillaries and induces glycoxidation. However, the detailed molecular mechanisms underlying the effects of high blood glucose on development of diabetic retinopathy have yet to be elucidated. In this study, we cultured a retinal pigmented epithelium cell line (ARPE-19) in mannitol-balanced 5.5 mM, 25 mM, and 100 mM d-glucose media, and evaluated protein expression and redox-regulation. We identified 56 proteins that showed significant changes in protein expression, and 33 proteins showing significant changes in thiol reactivity, in response to high glucose concentration. Several proteins that are involved in signal transduction, gene regulation, and transport showed significant changes in expression, whereas proteins involved in metabolism, transport, and cell survival displayed changes in thiol reactivity. Further analyses of clinical plasma specimens confirmed that the proteins lamin B2, PUMA, WTAP, ASGR1, and prohibitin 2 showed type 2 diabetic retinopathy-dependent alterations. In summary, in this study, we used a comprehensive retinal cell-based proteomic approach for the identification of changes in protein expression and redox-associated retinal markers induced by high glucose concentration. Some of the identified proteins have been validated with clinical samples and provide potential targets for the prognosis and diagnosis of diabetic retinopathy.
    No preview · Article · Oct 2012 · Molecular BioSystems
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    ABSTRACT: Diabetic retinopathy occurs in approximately 25% of patients with type 1 or type 2 diabetes; the disease can cause poor vision and even blindness because high glucose levels weaken retinal capillaries, causing leakage of blood into surrounding areas. We adopted a proteomics-based approach using 2D-DIGE and MALDI-TOF/TOF MS to compare the differential plasma proteome between diabetic retinopathy with significant retinopathy occurrence within 5 years after diagnosis of diabetes, and diabetic non-retinopathy without diagnosed retinopathy for more than 10 years after diagnosis of diabetes. We identified 77 plasma proteins, which represent 28 unique gene products. These proteins mainly have inflammatory response and coagulation roles. Our approach identified several potential diabetic retinopathy biomarkers including afamin and the protein arginine N-methyltransferase 5, which may be associated with the progression and development of diabetes. In conclusion, we report a comprehensive patient-based plasma proteomic approach to the identification of potential plasma biomarkers for diabetic retinopathy screening and detection.
    Full-text · Article · Dec 2012 · Archives of Biochemistry and Biophysics
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