Antagonizing Wnt Pathway in Diabetic Retinopathy

  1. Kang Zhang1,2,3
  1. 1Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  2. 2Department of Ophthalmology and Shiley Eye Center, and Institute for Genomic Medicine, University of California, San Diego, La Jolla, California
  3. 3Veterans Administration Healthcare System, San Diego, California
  1. Corresponding author: Kang Zhang, kang.zhang{at}gmail.com.

In this issue, Liu et al. (1) reported that kallistatin, an endogenous Wnt antagonist, exerted antiangiogenic and antineuroinflammatory effects by inhibiting canonical Wnt signaling in diabetic retinopathy (DR) mouse models.

DR is one of the most common microvascular complications of diabetes, characterized by retinal vascular leakage, inflammation, and abnormal neovascularization (2,3). DR has become the most frequent cause of blindness and loss of visual acuity among working adults in developed countries, and the incidence continues to rise (4). At present, laser photocoagulation and antivascular endothelial growth factor (anti-VEGF) therapies are standard-of-care treatment options. However, laser photocoagulation therapy only targets advanced stages of disease (5). Although anti-VEGF therapy can significantly inhibit vascular permeability and slow the progression of DR, recent clinical trials have showed that it is not effective for all patients and that some patients develop diminished responses to therapy after long-term use. Many patients can only benefit from a partial response to treatment. Additionally, anti-VEGF therapy results in some adverse events (6). Due to the limitations of current treatments, new strategies for DR therapy are urgently needed.

The pathology of DR is complex. A better understanding of the causative underlying mechanisms of DR is very important to find novel treatments. In addition to VEGF, a number of proangiogenic signaling pathways as well as inflammatory cytokines are linked to DR pathogenesis (6). Accumulating evidences have shown that the Wnt signaling pathway plays a fundamental role in multiple physiological and pathological processes, including angiogenesis and inflammation (710). Loss or gain of function of Wnt pathway components …

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