Cholesterol crystal formation is a unifying pathogenic mechanism in the development of diabetic retinopathy
نویسندگان
چکیده
Abstract Aims/hypothesis Hyper-reflective crystalline deposits found in retinal lesions have been suggested to predict the progression of diabetic retinopathy, but nature these structures remains unknown. Methods Scanning electron microscopy and immunohistochemistry were used identify cholesterol crystals (CCs) human donor, pig mouse tissue. The effects CCs analysed bovine endothelial cells vitro db / mice vivo using quantitative RT-PCR, bulk RNA sequencing, cell death permeability assays. Cholesterol homeostasis was determined 2 H O 7 -cholesterol. Results We identified hyper-reflective retina as CCs. Similarly, a model high-cholesterol diet-fed model. Cell culture studies demonstrated that treatment with can recapitulate all major pathogenic mechanisms leading including inflammation, breakdown blood–retinal barrier. Fibrates, statins α-cyclodextrin effectively dissolved present models prevented CC-induced pathology. Treatment reduced levels CC formation retina, retinopathy. Conclusions/interpretation established accumulation are unifying mechanism development Graphical
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It’s a great honor to join the exceptional club of Banting Award winners, many of whom were my role models and mentors. In addition, giving the Banting Lecture also has a very personal meaning to me, because without Frederick Banting, I would have died from type 1 diabetes when I was 8 years old. However, it was already apparent at the time I was diagnosed that for too many people like me, Bant...
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ژورنال
عنوان ژورنال: Diabetologia
سال: 2023
ISSN: ['1432-0428', '0012-186X']
DOI: https://doi.org/10.1007/s00125-023-05949-w