The following is a summary of “Evaluating lipid-lowering drug targets for full-course diabetic retinopathy,” published in the February 2025 issue of British Journal of Ophthalmology by Cao et al. 

Lipid control is considered a potential strategy to prevent diabetic retinopathy (DR) progression.  

Researchers conducted a retrospective study using Mendelian randomization (MR) to examine the causal relationship between lipid traits, lipid-lowering drug targets, and the progression of DR stages, including background, severe non-proliferative DR (NPDR), and proliferative DR (PDR) forms.  

They employed 2 -sample MR and drug target MR to explore the causal effects of lipid traits and lipid-lowering drug targets on full-course DR (background DR, severe NPDR, and PDR). Genetic variants related to lipid traits and genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium and UK Biobank. Summary-level data on full-course DR were obtained from FinnGen.  

The results showed no significant causal link between lipid traits and full-course DR. However, drug target MR analysis revealed that enhancing peroxisome proliferator-activated receptor gamma (PPARG) was linked to a reduced risk of background DR [OR]=0.12, P =0.005) and PDR (OR=0.25, P =0.006). Mediation MR analysis further indicated that reduced fasting insulin (P =0.015) and HbA1c (P =0.005) levels accounted for most of the association between PPARG and full-course DR.  

Investigators concluded that PPARG might have been a promising drug target for full-course DR, with its activation potentially reducing the risk, particularly of background DR and PDR, possibly through a glucose-lowering effect. 

Source: bjo.bmj.com/content/early/2025/02/02/bjo-2024-325771