ArticleDiabetologia2019
Anti-fumarase antibody promotes the dropout of photoreceptor inner and outer segments in diabetic macular oedema.
Article in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- The association of islet autoantibodies with the neural retinal thickness and microcirculation in type 1 diabetes mellitus with no clinical evidence of diabetic retinopathy.Acta diabetologica · 2024Article
- Pathological Neurovascular Unit Mapping onto Multimodal Imaging in Diabetic Macular Edema.Medicina (Kaunas, Lithuania) · 2023Review
- Identification of key genes modules linking diabetic retinopathy and circadian rhythm.Frontiers in immunology · 2023Article
- Correlation of photoreceptor damage with anti-retina antibodies level in aqueous humor in macular edema patients.Scientific reports · 2022Article
- Comparison of clinical characteristics in patients with acute zonal occult outer retinopathy according to anti-retinal antibody status.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Observational
- Multiple Bioinformatics Analyses of Integrated Gene Expression Profiling Data and Verification of Hub Genes Associated with Diabetic Retinopathy.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The Role of Inflammation in Diabetic Retinopathy.Frontiers in immunology · 2020Review
- Anti-Hexokinase 1 Antibody as a Novel Serum Biomarker of a Subgroup of Diabetic Macular Edema.Scientific reports · 2019Observational
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
aims/hypothesisIn diabetic macular oedema (DMO), blood components passing through the disrupted blood-retinal barrier cause neuroinflammation, but the mechanism by which autoantibodies induce neuroglial dysfunction is unknown. The aim of this study was to identify a novel autoantibody and to evaluate its pathological effects on clinically relevant photoreceptor injuries.
methodsBiochemical purification and subsequent peptide fingerprinting were applied to identify autoantigens. The titres of autoantibodies in DMO sera were quantified and their associations with clinical variables were evaluated. Two animal models (i.e. passive transfer of autoantibodies and active immunisation) were characterised with respect to autoimmune mechanisms underlying photoreceptor injuries.
resultsAfter screening serum IgG from individuals with DMO, fumarase, a Krebs cycle enzyme expressed in inner segments, was identified as an autoantigen. Serum levels of anti-fumarase IgG in participants with DMO were higher than those in diabetic participants without DMO (p < 0.001) and were related to photoreceptor damage and visual dysfunction. Passively transferred fumarase IgG from DMO sera in concert with complement impaired the function and structure of rodent photoreceptors. This was consistent with complement activation in the damaged photoreceptors of mice immunised with fumarase. Fumarase was recruited to the cell surface by complement and reacted to this autoantibody. Subsequently, combined administration of anti-fumarase antibody and complement elicited mitochondrial disruption and caspase-3 activation. CONCLUSIONS/
interpretationThis study has identified anti-fumarase antibody as a serum biomarker and demonstrates that the generation of this autoantibody might be a pathological mechanism of autoimmune photoreceptor injuries in DMO.
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