Cholesterol crystal formation is a unifying pathogenic mechanism in the development of diabetic retinopathy – published online 14/06/2023

Sandra S. Hammer, Tim F. Dorweiler, Delaney McFarland, Yvonne Adu‑Agyeiwaah, Natalia Mast, Nicole El‑Darzi, Seth D. Fortmann, Sunil Nooti, Devendra K. Agrawal, Irina A. Pikuleva, George S. Abela, Maria B. Grant, Julia V. Busik

With the advancement of spectral-domain optical coherence tomography imaging, hyperreflective crystalline deposits have been identified in retinal pathologies, including diabetic retinopathy. In this issue, Hammer and Dorweiler et al (https://doi.org/10.1007/s00125-023-05949-w) uncover the nature of crystalline deposits in retina from human donors with diabetes as cholesterol crystals. Using cell culture- and animal model-based studies, cholesterol crystals were shown to recapitulate all major pathogenic mechanisms leading to diabetic retinopathy, including inflammation, cell death and breakdown of the blood–retinal barrier. Fibrates, statins and α-cyclodextrin effectively dissolved cholesterol crystals and prevented endothelial pathology. The authors conclude that the formation of cholesterol crystals represents a unifying pathogenic mechanism in the development of diabetic retinopathy and strategies for removal of cholesterol crystals may have therapeutic value in the treatment of diabetic retinopathy.

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