Vitreous from patients with proliferative diabetic retinopathy induced changes in neutrophil activation markers.

Patients with PDR and DME had increased neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) values compared with controls.

• Elevated NLR and MLR values were found in both PDR (n=15) and DME (n=8) patient groups compared to surrogate controls (n=8).
• The difference in NLR and MLR between patient groups and controls was statistically significant (p < 0.05).
• Controls consisted of patients with rhegmatogenous retinal detachment (n=5) and macular hole (n=3).

Vitreous humor from patients with PDR showed a twofold increase in the inflammatory cytokines CCL2, CXCL5, and angiogenin compared to controls.

• Cytokine levels were measured using an angiogenic cytokine protein array at a vitreous protein concentration of 250 mg/ml.
• Cytokine levels were normalized to those of surrogate controls and fold changes were calculated.
• The twofold increase was specific to PDR vitreous; DME vitreous results for these cytokines were not described as reaching the same threshold.
• CCL2, CXCL5, and angiogenin are identified as potential therapeutic targets for PDR based on these findings.

PDR vitreous humor significantly downregulated neutrophil activation markers CD11b and CD15 compared to control vitreous humor.

• Peripheral blood was incubated with diluted vitreous from different conditions and neutrophil activation markers were assessed via flow cytometry.
• CD11b and CD15 expression were both significantly reduced when neutrophils were exposed to PDR vitreous (p < 0.05).
• CD66b expression remained unchanged following exposure to PDR vitreous (p > 0.05).
• This downregulation of activation markers suggests the presence of immunosuppressive or exhaustion-inducing factors in PDR vitreous.

DME vitreous did not significantly change any of the analyzed neutrophil activation markers (CD15, CD11b, or CD66b).

• In vitro neutrophil stimulation with DME vitreous (from n=8 patients) did not produce significant changes in CD11b, CD15, or CD66b expression.
• This contrasts with PDR vitreous, which significantly downregulated CD11b and CD15.
• The finding suggests differential effects of DME versus PDR vitreous on neutrophil function.

Systemic immune-inflammation indices including platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio are useful predictors of diabetes mellitus-related diseases and inflammatory complications.

• These indices are described as systemic markers relevant to DR pathogenesis.
• Cumulative evidence indicates a concentration of inflammatory mediators in the vitreous humor, making its analysis a valuable tool for investigating retinal complications.
• Both systemic and local inflammatory molecules and immune cells, particularly neutrophils, play crucial roles in DR pathogenesis.