Cytokines and the Pathogenesis of Macular Edema in Branch Retinal Vein Occlusion

Abstract

Branch retinal vein occlusion (BRVO) is a very common retinal vascular problem in patients with lifestyle-related diseases, such as hypertension and arteriosclerosis. In patients with BRVO, development of macular edema is the main cause of visual impairment. BRVO is still a controversial condition in many respects. Over the years, various methods such as laser photocoagulation have been tried to treat macular edema associated with BRVO, but the results were not satisfactory. After vascular endothelial growth factor (VEGF) was found to have an important role in the pathogenesis of macular edema in BRVO patients, treatment of this condition was revolutionized by development of anti-VEGF therapy. Although macular edema improves dramatically following intraocular injection of anti-VEGF agents, repeated recurrence and resistance of edema is a major problem in some BRVO patients. This suggests that factors or cytokines other than VEGF may be associated with inflammation and retinal hypoxia in BRVO and that the pathogenesis of macular edema is complicated. The present review assesses the role of various factors and cytokines in the pathogenesis of macular edema associated with BRVO. We present a mechanism that is not only plausible but should also be useful for developing new therapeutic strategies.

Relationship between distribution and severity of non-perfusion and cytokine levels and macular thickness in branch retinal vein occlusion

“…In particular, the aqueous levels of Ang-2, MCP-1, IL-8, PlGF, and VEGF-A showed significant correlation with CMT. In the presence of VEGF-A, Ang-2 promotes angiogenesis and vascular sprouting and MCP-1promotes chemotaxis and adhesion of leukocytes along with a decrease of local blood flow velocity and create positive feedback loop, which further promotes retinal hypoxia 6 , 21 . IL-8 promotes the upregulation of VEGF and links the inflammatory process with angiogenesis 2 .…”

“…Capture bead kits (Beadlyte, Upstate Biotechnology, Lake Placid, NY, USA) were used for the detection of Ang-1, Ang-2, MCP-1, IL-6, IL-8, PDGF-AA, PlGF, and VEGF-A. These particular cytokines were pre-specified as they are known to be angiogenic or pro-inflammatory, and have been suggested to be relevant to macular edema [2][3][4][5][6] . The concentrations of cytokines were calculated in duplicate from the standard curves of each cytokine tested using the Master Plex QT 2010 software (Miraibio, Hitachi, CA, USA).…”

“…Noma et al reported that vitreous fluid levels of VEGF, sICAM-1, IL-6, MCP-1, and PTX3 showed significant correlation with NPA in BRVO 3 . The extent of retinal ischemia and concentrations of cytokines in patients with BRVO has also been correlated with the clinical course and response to the treatment 2 – 6 , suggesting a potential prognostic role for these biomarkers.…”

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study

“…1 Important elements in the development of macular edema secondary to BRVO include vascular endothelial growth factor (VEGF), VEGF receptor-1 and 2, as well as an inflammatory response mediated by interleukin-6, interleukin-8, monocyte chemoattractant protein 1, and platelet-derived growth factor. [2][3][4][5][6][7][8][9][10] Although this subset of proteins is well-characterized in BRVO, there is very limited knowledge about large-scale intraocular protein changes in samples from humans with BRVO. 11 Large-scale protein analyses are effectively performed with mass spectrometry-based proteomic techniques, which aim at identifying and quantifying the entire set of proteins in a given tissue or body fluid.…”

Higher aqueous levels of matrix metalloproteinases indicated visual impairment in patients with retina vein occlusion after anti-VEGF therapy

“…Retinal vein thrombosis disrupts upstream blood circulation leading to interstitial fluid and protein accumulation, microcirculatory ischemia and tissue edema(20,21). The inflammatory response induced by vascular occlusion further damages retinal vasculature and neurons and accelerates disease progression(22).MMPs are a class of zinc-dependent proteases that are involved in the degradation of ECM proteins. There are 28 members of the MMP family, of which 14 are expressed in human vascular tissues and cells, including vascular smooth muscle (VSM), fibroblasts and leukocytes (23).…”