| Title |
Antagonising Wnt/β-catenin signalling ameliorates lens-capsulotomy-induced retinal degeneration in a mouse model of diabetes
|
|---|---|
| Published in |
Diabetologia, July 2018
|
| DOI | 10.1007/s00125-018-4682-3 |
| Pubmed ID | |
| Authors |
Jose R. Hombrebueno, Imran H. A. Ali, Jian-xing Ma, Mei Chen, Heping 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) (Mab2F1; 5 μg/μl in each eye). Lens capsulotomy triggered the early onset of retinal neurodegeneration in Ins2Akita mice, evidenced by abnormal scotopic a- and b-wave responses, reduced retinal thickness and degeneration of outer/inner retinal neurons. Diabetic Ins2Akita mice also had a higher number of infiltrating ionised calcium-binding adapter molecule 1 (IBA1)/CD68+ cells in the anterior/posterior ocular tissues and increased retinal expression of inflammatory mediators (chemokine [C-C motif] ligand 2 [CCL2] and IL-1β). The expression of β-catenin was significantly increased in the inner nuclear layer, ganglion cells and infiltrating immune cells in Ins2Akita mice receiving capsulotomy. Neutralisation of Wnt/β-catenin signalling by Mab2F1 ameliorated ocular inflammation and prevented capsulotomy-induced retinal degeneration in the Ins2Akita mouse model of diabetes. Targeting the canonical Wnt/β-catenin signalling pathway may provide a novel approach for the postoperative management of diabetic individuals needing cataract surgery. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Chile | 1 | 25% |
| United Kingdom | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 4 | 20% |
| Student > Ph. D. Student | 4 | 20% |
| Student > Postgraduate | 2 | 10% |
| Researcher | 2 | 10% |
| Student > Doctoral Student | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 5 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 25% |
| Neuroscience | 2 | 10% |
| Nursing and Health Professions | 1 | 5% |
| Agricultural and Biological Sciences | 1 | 5% |
| Biochemistry, Genetics and Molecular Biology | 1 | 5% |
| Other | 4 | 20% |
| Unknown | 6 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 July 2018.
All research outputs
#15,014,589
of 23,096,849 outputs
Outputs from Diabetologia
#4,446
of 5,096 outputs
Outputs of similar age
#179,452
of 296,625 outputs
Outputs of similar age from Diabetologia
#64
of 66 outputs
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