Bone Morphogenetic Proteins and Diabetic Retinopathy

Abstract

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others' studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

Keywords: BMP2; BMP4; age-related macular degeneration; bone morphognetic proteins; diabetic retinopathy.

Figure 1

BMP signaling pathway involves both a canonical (SMAD-dependent) and a non-canonical (non-SMAD-dependent) pathway.

Figure 2

The blood-retinal barrier (BRB) is formed by an inner blood retinal barrier (iBRB) and an outer blood retinal barrier (oBRB). The inner barrier is maintained via tight junctions among retinal non-fenestrated endothelial cells. The outer blood-retinal barrier is maintained via tight junctions among retinal pigment epithelial cells (RPE). Different BMPs contribute to retinal barrier dysfunction. Our studies show the BMP2 affecting the iBRB, while changes in circulating BMP4 levels contributed to the oBRB dysfunction.