Retinal angiogenic diseases (RADs) are the leading cause of visual impairment in working adults. RADs included conditions such as age-related macular degeneration, diabetic macular edema, and diabetic retinopathy. These diseases are asymptomatic in the early stages, contributing to the difficulty in diagnosis and treatment. Vascular abnormalities including microaneurysms, dot hemorrhages and neovascularization are central themes of RADs [1]. Therefore, therapies such as intravitreal injection of anti-VEGF drugs and laser photocoagulation surgery are targeted to halt disease progression only in the advanced stages of the diseases. However, approximately 50% of patients do not respond, and often require multiple treatments. There is no current treatment for the early stage of RADs. Hence there is an urgent need to understand the components involved in vascular angiogenesis, specifically the extracellular matrix (ECM) which contributes to the integrity of the microvasculature in the retina.Decorin (Dcn) is a small leucine-rich proteoglycan (SLRP) with multiple functions. It is involved in fibrillogenesis and regulation of ECM mechanical properties by binding and interacting with their major components. Dcn is also involved in modulating inflammation as it binds to Toll-like receptor 4 (TLR4) and sequesters proinflammatory cytokine -TNF and growth factors such as transforming growth factor beta (TGF) [2,3]. Furthermore, evidence shows that Dcn abrogates angiogenesis by direct inhibition of vascular endothelial receptor 2 (VEGFR2) [4]. In the retina, Dcn plays a key role as a neurotrophic factor during retinal differentiation [5], and localizes to nerve fiber layer and ganglion cell layer in the mature retina [6]. Upon retinal injury in mice, Dcn was shown to be highly upregulated in the inner retinal layers [7], while treatment with decorin was shown to improve vitrectomy outcome in rabbits with proliferative vitreoretinopathy [8], and prevent loss of tight junctions in human retinal pigmented epithelial cells under hyperglycemic and hypoxia stress [9]. Taken together, results indicate Dcn to be actively involved in retinal repair. However, its function in the maintenance of adult retinal microvasculature is not known. Hence this study uses Dcn knockout (Dcn -/-) mice to elucidate the functional role of Dcn in preserving the neuronal structural integrity and spatial organization in a retinal microvasculature.Eight to twelve weeks old Dcn -/-mice retina were photographed using fundus photography and fundus fluorescein angiography. Animals were sacrificed and eyes enucleated for analysis. Eyes were fixed in paraformaldehyde (PFA), dehydrated and embedded in paraffin for histological examination. Retina fixed in formalin were isolated from eyecups and subjected to trypsin digestion to visualize the intact retinal vasculature. Retinal flat-mount staining with isolectin GS-IB4 was performed to examine capillary integrity. Electron microscopy was used for ultrastructural investigation of retinal and neuronal cells. For ...