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Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic

Yaqi Bai1, Yujia Xi2, Chenwei Gui3

  • 1The First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China.

Translational Vision Science & Technology
|May 2, 2025
PubMed
Abstract

Insights

Higher serum eIF4E levels promote diabetic retinopathy (DR) progression. This study suggests targeting eIF4E may offer a new therapeutic strategy for DR, a condition linked to mTOR signaling.

Area of Science:

  • Ophthalmology
  • Genetics
  • Molecular Biology

Background:

  • The mechanistic target of rapamycin (mTOR) pathway is crucial in diabetic retinopathy (DR) development.
  • The specific roles of mTORC1 downstream proteins in DR pathogenesis are not fully understood.

Purpose of the Study:

  • To investigate the causal relationship between mTORC1 downstream proteins and the risk of diabetic retinopathy (DR).
  • To assess the potential of targeting these proteins for DR treatment.

Main Methods:

  • Employed Mendelian randomization (MR) using summary statistics from the INTERVAL and FinnGen studies.
  • Utilized inverse-variance-weighted, weighted median, and MR-Egger methods.
  • Conducted sensitivity analyses to detect pleiotropy and heterogeneity.

Main Results:

  • Elevated genetically predicted eukaryotic initiation factor 4E (eIF4E) showed a positive correlation with DR risk (OR = 1.057, P = 0.022).
  • No significant associations were found for RP-S6K, eIF4G, eIF4A, eIF4E-BP, or eIF4B with DR.
  • Sensitivity analyses indicated no significant heterogeneity or pleiotropy.

Conclusions:

  • Increased serum eIF4E levels are implicated in promoting diabetic retinopathy progression.
  • Pharmacological inhibition of eIF4E presents a potential therapeutic avenue for DR treatment.
  • This research establishes eIF4E as a key factor in DR development, guiding future research into novel therapeutic targets.

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