Antagonising Wnt/β-catenin signalling ameliorates lens-capsulotomy-induced retinal degeneration in a mouse model of diabetes

Diabetologia
Jose R HombrebuenoHeping Xu

Abstract

Cataract surgery in diabetic individuals worsens pre-existing retinopathy and triggers the development of diabetic ocular complications, although the underlying cellular and molecular pathophysiology remains elusive. We hypothesise that lens surgery may exaggerate pre-existing retinal inflammation in diabetes, which may accelerate neurovascular degeneration in diabetic eyes. Male heterozygous Ins2Akita mice (3 months of age) and C57BL/6 J age-matched siblings received either lens capsulotomy (to mimic human cataract surgery) or corneal incision (sham surgery) in the right eye. At different days post surgery, inflammation in anterior/posterior ocular tissues was assessed by immunohistochemistry and proinflammatory gene expression in the retina by quantitative PCR (qPCR). Degenerative changes in the retina were evaluated by electroretinography, in vivo examination of retinal thickness (using spectral domain optical coherence tomography [SD-OCT]) and morphometric analysis of retinal neurons. The therapeutic benefit of neutralising Wnt/β-catenin signalling following lens capsulotomy was evaluated by intravitreal administration of monoclonal antibody against the co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) (...Continue Reading

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Methods Mentioned

BETA
PCR
confocal microscopy
light microscopy

Software Mentioned

FIJI
GraphPad

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