Methylglyoxal induces retinopathy-type lesions in the absence of hyperglycemia

• Verfasst von: Schlotterer, Andrea [VerfasserIn]
• Verfasst von: Kolibabka, Matthias [VerfasserIn]
• Verfasst von: Lin, Jihong [VerfasserIn]
• Verfasst von: Dietrich, Nadine [VerfasserIn]
• Verfasst von: Sticht, Carsten [VerfasserIn]
• Verfasst von: Fleming, Thomas [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Hammes, Hans-Peter [VerfasserIn]
• Titel: Methylglyoxal induces retinopathy-type lesions in the absence of hyperglycemia
• Titelzusatz: studies in a rat model
• Verf.angabe: Andrea Schlotterer, Matthias Kolibabka, Jihong Lin, Kübra Acunman, Nadine Dietrich, Carsten Sticht, Thomas Fleming, Peter Nawroth, Hans-Peter Hammes
• E-Jahr: 2019
• Jahr: 27 Feb 2019
• Umfang: 13 S.
• Fussnoten: Gesehen am 01.04.2019
• Titel Quelle: Enthalten in: Federation of American Societies for Experimental BiologyThe FASEB journal
• Ort Quelle: Hoboken, NJ : Wiley, 1987
• Jahr Quelle: 2019
• Band/Heft Quelle: 33(2019), 3, Seite 4141-4153
• ISSN Quelle: 1530-6860
• DOI: doi:10.1096/fj.201801146RR
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1662623607

Abstract

The aim of this study was to evaluate whether damage to the neurovascular unit in diabetes depends on reactive metabolites such as methylglyoxal (MG), and to assess its impact on retinal gene expression. Male Wistar rats were supplied with MG (50 mM) by drinking water and compared with age-matched streptozotocin-diabetic animals and untreated controls. Retinal damage was evaluated for the accumulation of MG-derived advanced glycation end products, changes in hexosamine and PKC pathway activation, microglial activation, vascular alterations (pericyte loss and vasoregression), neuroretinal function assessed by electroretinogram, and neurodegeneration. Retinal gene regulation was studied by microarray analysis, and transcription factor involvement was identified by upstream regulator analysis. Systemic application of MG by drinking water increased retinal MG to levels comparable with diabetic animals. Elevated retinal MG resulted in MG-derived hydroimidazolone modifications in the ganglion cell layer, inner nuclear layer, and outer nuclear layer, a moderate activation of the hexosamine pathway, a pan-retinal activation of microglia, loss of pericytes, increased formation of acellular capillaries, decreased function of bipolar cells, and increased expression of the crystallin gene family. MG mimics important aspects of diabetic retinopathy and plays a pathogenic role in microglial activation, vascular damage, and neuroretinal dysfunction. In response to MG, the retina induces expression of neuroprotective crystallins.—Schlotterer, A., Kolibabka, M., Lin, J., Acunman, K., Dietrich, N., Sticht, C., Fleming, T., Nawroth, P., Hammes, H.-P. Methylglyoxal induces retinopathy-type lesions in the absence of hyperglycemia: studies in a rat model.