Role of Soluble Vascular Endothelial Growth Factor Receptor Signaling and Other Factors or Cytokines in Central Retinal Vein Occlusion With Macular Edema

Abstract

PURPOSE: The association between aqueous humor levels of various growth/inflammatory factors or cytokines and the severity of macular edema was investigated in patients with central retinal vein occlusion (CRVO). METHODS: Aqueous humor levels of 11 factors or cytokines were measured in CRVO patients with macular edema (n = 38) and in cataract patients (n = 15) as controls. Aqueous humor samples were obtained from the patients during surgery and the levels of VEGF, its receptors, and other factors or cytokines were measured by the suspension array method. The severity of macular edema was determined by measuring the central macular thickness, neurosensory retinal thickness, and subfoveal serous retinal thickness with optical coherence tomography. RESULTS: Aqueous humor levels of growth factors, soluble VEGF receptor 1 (sVEGFR-1), sVEGFR-2, and inflammatory factors or cytokines were significantly higher in the CRVO group than in the control group. The aqueous level of sVEGFR-1 was significantly correlated with the neurosensory retinal thickness, as well as with the levels of growth factors (VEGF, placental growth factor, and platelet-derived growth factor-AA) and inflammatory factors/cytokines (monocyte chemotactic protein-1, interleukin-6, and interleukin-8). Aqueous humor levels of the three growth factors also were significantly correlated with each other, as were levels of the two sVEGFRs. CONCLUSIONS: These findings suggest that growth/inflammatory factors and cytokines have an important role in macular edema associated with CRVO. Better understanding of the mechanisms involved may lead to development of new treatments, such as anti-VEGFR-1 therapy.