Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.

The Lymphatic System in Obesity, Insulin Resistance, and Cardiovascular Diseases

“…A follow-up study demonstrated that soluble pro-growth factors in vitreous fluid promoted lymphatic sprouting of patient-derived tissues with diabetic retinopathy (Gucciardo et al, 2018a), further supporting the notion that the microenvironment of the eyes of diabetic retinopathy contains sufficient cue for abnormal lymphatic expansion. Pathological lymphangiogenesis observed in the eyes of diabetic retinopathy may, therefore, be regarded as a feature for therapeutic targeting (Yang et al, 2016; Gucciardo et al, 2018b). Ongoing clinical trials targeting VEGFR- or RTK-mediated signaling may provide possibilities to suppress pathological lymphatic overgrowth, but identification of novel lymphatic specific targets is probably necessary for better therapeutic outcomes (Williams et al, 2010).…”

Causal effects of gut microbiota on diabetic retinopathy: A Mendelian randomization study

“…As a microvascular diabetic complication, diabetic retinopathy (DR) is one of the most prevalent metabolic and blinding eye diseases in ophthalmology ( 2 ). Current research indicates that the complex mechanism of DR involves the interaction of multiple factors, including genetics, angiogenesis, immunity, inflammatory injury, and neurodegeneration ( 3 ). Therefore, researchers have proposed and developed more targeted treatment and prevention approaches.…”

The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells

“…It is physiologically required for regulating proliferation and assembling endothelial cells during vasculogenesis, as well as for their maintenance and survival throughout the lifetime of blood vessels [23]. However, under subtle pathological alterations, abnormal angiogenesis with retinal and choroidal microvascular alterations have been observed during PDR, high myopia, and neovascular AMD [24][25][26].…”