Diabetic retinopathy (DR) is one of the very serious and potentially blinding complications of diabetes and is the leading cause of blindness in people of working age. The mechanisms underlying the development of DR have been completely elucidated. DR shares many characteristics of a low-grade inflammatory disease, such as increased levels of proinflammatory cytokines in the retina and vitreous and increased permeability of retinal capillaries that become nonperfused and ischemic. Moreover, the development of diabetic complications is related to the elevated level of complement and may be used as new therapeutic targets. Further, the mannose-binding lectin pathway, an overall regulatory component of the complement system, has been found to be directly involved in the development of diabetic angiopathy.

As members of the mannose-binding lectin, ficolins also are known to activate the lectin pathway of complement. The 3 ficolins that have been identified in humans are M-ficolin, L-ficolin, and H-ficolin (referred to as ficolin-1, ficolin-2, and ficolin-3, respectively). On recognition of the infectious agent, ficolins act through 2 distinct routes: they initiate the lectin pathway of complement activation through attached serine proteases and they act through a primitive opsonophagocytosis, thus limiting the infection and concurrently orchestrating the subsequent adaptive clonal immune response. The dysfunction or abnormal expression of ficolins may play a crucial role in the pathogenesis of human diseases, including infectious and inflammatory diseases such as recurrent respiratory infections, autoimmune disease resulting from apoptosis, systemic lupus erythematosus, immunoglobulin A nephropathy, and the clinical syndrome of pre-eclampsia. Recently, using a proteomic approach, we found that ficolin-3 was upregulated significantly in the serum of type 2 diabetic patients ( P = .012).

Vascular endothelial growth factor (VEGF) plays a major role in the initiation and development of DR. VEGF levels also are reported to be elevated in patients with proliferative diabetic retinopathy (PDR). Our previous study uncovered that VEGF itself produces many of the vascular abnormalities common to DR, such as the increase in cellular apoptosis and permeability. In contrast, pigment epithelium-derived factor (PEDF), a potent inhibitor of inflammatory and angiogenesis, has been found to be involved in the pathogenesis of PDR. Gao and Zheng and associates reported that the time course of the VEGF-to-PEDF ratio change correlated with the development and progression of retinal neovascularization; the VEGF-to-PEDF ratio represented a dynamic balance between angiogenic stimulators and inhibitors, and any disturbance of the balance seems to play a key role in the pathogenesis of DR.

These findings prompted us to examine whether ficolin-3 plays a role in the exacerbation of DR in cooperation with VEGF and PEDF. To the best of our knowledge, this is the first investigation of the involvement of ficolin-3 with inflammatory and angiogenic factors, VEGF and PEDF, in the vitreous of eyes with PDR. Analysis of the vitreous fluid allowed us to clarify the correlation between ficolin-3 and the VEGF-to-PEDF ratio in the pathogenesis of PDR.