Investigative ophthalmology & visual science · 2019
Transducin1, Phototransduction and the Development of Early Diabetic Retinopathy.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Liu Haitao, Tang Jie, Du Yunpeng, Saadane Aicha, Samuels Ivy, Veenstra Alex, Kiser Jianying Z, Palczewski Krzysztof, Kern Timothy S
Аннотация
PURPOSE: Recent evidence suggests that retinal photoreceptor cells have an important role in the pathogenesis of retinal microvascular lesions in diabetes. We investigated the role of rod cell phototransduction on the pathogenesis of early diabetic retinopathy (DR) using Gnat1-/- mice (which causes permanent inhibition of phototransduction in rod cells without degeneration).
METHODS: Retinal thickness, oxidative stress, expression of inflammatory proteins, electroretinograms (ERG) and optokinetic responses, and capillary permeability and degeneration were evaluated at up to 8 months of diabetes.
RESULTS: The diabetes-induced degeneration of retinal capillaries was significantly inhibited in the Gnat1-/- diabetics. The effect of the Gnat1 deletion on the diabetes-induced increase in permeability showed a nonuniform accumulation of albumin in the neural retina; the defect was inhibited in diabetic Gnat1-/- mice in the inner plexiform layer (IPL), but neither in the outer plexiform (OPL) nor inner nuclear (INL) layers. In Gnat1-deficient animals, the diabetes-induced increase in expression of inflammatory associated proteins (iNOS and ICAM-1, and phosphorylation of IĸB) in the retina, and the leukocyte mediated killing of retinal endothelial cells were inhibited, however the diabetes-mediated induction of oxidative stress was not inhibited.
CONCLUSIONS: In conclusion, deletion of transducin1 (and the resulting inhibition of phototransduction in rod cells) inhibits the development of retinal vascular pathology in early DR.
METHODS: Retinal thickness, oxidative stress, expression of inflammatory proteins, electroretinograms (ERG) and optokinetic responses, and capillary permeability and degeneration were evaluated at up to 8 months of diabetes.
RESULTS: The diabetes-induced degeneration of retinal capillaries was significantly inhibited in the Gnat1-/- diabetics. The effect of the Gnat1 deletion on the diabetes-induced increase in permeability showed a nonuniform accumulation of albumin in the neural retina; the defect was inhibited in diabetic Gnat1-/- mice in the inner plexiform layer (IPL), but neither in the outer plexiform (OPL) nor inner nuclear (INL) layers. In Gnat1-deficient animals, the diabetes-induced increase in expression of inflammatory associated proteins (iNOS and ICAM-1, and phosphorylation of IĸB) in the retina, and the leukocyte mediated killing of retinal endothelial cells were inhibited, however the diabetes-mediated induction of oxidative stress was not inhibited.
CONCLUSIONS: In conclusion, deletion of transducin1 (and the resulting inhibition of phototransduction in rod cells) inhibits the development of retinal vascular pathology in early DR.
Предметные рубрики MeSH
AnimalsCapillary PermeabilityDiabetes Mellitus, ExperimentalDiabetic RetinopathyElectroretinographyGTP-Binding Protein alpha SubunitsGene DeletionI-kappa B ProteinsImmunoblottingIntercellular Adhesion Molecule-1MaleMiceMice, Inbred C57BLMice, Mutant StrainsNitric Oxide Synthase Type IINystagmus, OptokineticOxidative StressPhosphorylationRetinal Rod Photoreceptor CellsRetinal VesselsStreptozocinTomography, Optical CoherenceTransducinVision, Ocular