Systemic inflammatory regulators and proliferative diabetic retinopathy: A bidirectional Mendelian randomization...

Area of Science:

• Ophthalmology
• Immunology
• Genetics

Background:

• Systemic inflammation is increasingly recognized as a critical mechanism in proliferative diabetic retinopathy (PDR).
• The specific systemic inflammatory factors driving PDR pathogenesis have remained largely unidentified.
• This study aimed to elucidate the upstream and downstream systemic regulators of PDR using Mendelian randomization (MR).

Approach:

• A bidirectional two-sample MR analysis was conducted using genome-wide association study data for 41 serum cytokines and PDR.
• Data included Finnish individuals and cohorts of European ancestry, with results pooled via meta-analysis.
• Multiple MR methods and sensitivity analyses were employed to ensure robustness.

Key Points:

• Genetically predicted higher levels of stem cell growth factor-β (SCGFb) and interleukin-8 were associated with an increased risk of PDR.
• A one SD increase in SCGFb and interleukin-8 corresponded to an 11.8% and 21.4% higher PDR risk, respectively.
• PDR predisposition was linked to elevated levels of growth-regulated oncogene-α (GROa), SDF1a, MCP3, GCSF, IL-12p70, and IL-2ra.

Conclusions:

• The MR study identified two upstream regulators and six downstream effectors of PDR.
• These findings offer potential targets for novel therapeutic strategies for PDR.
• Further validation in larger cohorts is necessary to confirm these associations.