Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus and remains a leading cause of blindness. Increased vascular permeability caused by breakdown of the blood-retinal barrier (BRB), a characteristic sign of early DR, results in diabetic macular edema (DME), which is a major cause of visual impairment in diabetic patients. Several cellular mechanisms and molecular pathways activated by hyperglycemia and/or hypoxia have been demonstrated to be involved in promoting BRB breakdown in diabetes. Ischemia-induced retinal angiogenesis, inflammation and fibrosis are present in the ocular microenvironment of patients with proliferative diabetic retinopathy (PDR) and these are critical mechanisms for PDR initiation and progression. The outgrowth of fibrovascular epiretinal membranes at the vitreoretinal interface often leads to catastrophic visual loss due to vitreous hemorrhage and/or traction retinal detachment. In addition, evidence exists that retinal neurodegeneration develops before visible microvascular abnormalities. Increasing evidence points to inflammation as a critical contributor to the development of DR. Recent data support a causal relationship between persistent inflammation and altered neuroretinal function, increased retinal vascular permeability and development of retinal neovascularization. Therefore, an emerging issue in DR research is the identification of the molecular links between inflammation and development of DR and the development of new concepts for treatments acting on inflammatory processes. The involved cellular processes are promoted by local production of growth factors, proinflammatory cytokines, chemokines, adhesion molecules, matrix metalloproteinases and their corresponding receptors. Of the many factors produced in the ocular microenvironment of patients with DR, vascular endothelial growth factor (VEGF) plays a pivotal role in promoting breakdown of the BRB and retinal neovascularization. However, angiogenesis depends on multiple factors, and when the activity of one angiogenic factor such as VEGF is suppressed, the expression of other angiogenic factors may be upregulated, leading to compensation and limiting the efficacy of anti-VEGF treatment. In addition, many patients with DME do not show complete resolution of edema despite multiple intravitreal injections of anti-VEGF drugs. Moreover, in those patients who respond, the effect might be transient. This underlines the need for additional therapies.
The fact that a substantial proportion of patients fails to respond to anti-VEGF monotherapy suggests that factors other than VEGF may be important in this disease. Therefore, the aims are to broaden general knowledge about DR on the basis of recent laboratory and clinical findings and to identify novel key pathways that drive DR initiation and progression to find innovative therapeutic strategies.
This Research Topic welcomes the submission of manuscripts focusing on, but not limited to, the following areas:
• Identification of additional therapeutic targets, creating the possibility to inhibit different pathways simultaneously
• Targeting novel factors, preferably with VEGF-independent signaling pathways
• Innovative neuroprotective treatment strategies
• Novel drug delivery systems
Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus and remains a leading cause of blindness. Increased vascular permeability caused by breakdown of the blood-retinal barrier (BRB), a characteristic sign of early DR, results in diabetic macular edema (DME), which is a major cause of visual impairment in diabetic patients. Several cellular mechanisms and molecular pathways activated by hyperglycemia and/or hypoxia have been demonstrated to be involved in promoting BRB breakdown in diabetes. Ischemia-induced retinal angiogenesis, inflammation and fibrosis are present in the ocular microenvironment of patients with proliferative diabetic retinopathy (PDR) and these are critical mechanisms for PDR initiation and progression. The outgrowth of fibrovascular epiretinal membranes at the vitreoretinal interface often leads to catastrophic visual loss due to vitreous hemorrhage and/or traction retinal detachment. In addition, evidence exists that retinal neurodegeneration develops before visible microvascular abnormalities. Increasing evidence points to inflammation as a critical contributor to the development of DR. Recent data support a causal relationship between persistent inflammation and altered neuroretinal function, increased retinal vascular permeability and development of retinal neovascularization. Therefore, an emerging issue in DR research is the identification of the molecular links between inflammation and development of DR and the development of new concepts for treatments acting on inflammatory processes. The involved cellular processes are promoted by local production of growth factors, proinflammatory cytokines, chemokines, adhesion molecules, matrix metalloproteinases and their corresponding receptors. Of the many factors produced in the ocular microenvironment of patients with DR, vascular endothelial growth factor (VEGF) plays a pivotal role in promoting breakdown of the BRB and retinal neovascularization. However, angiogenesis depends on multiple factors, and when the activity of one angiogenic factor such as VEGF is suppressed, the expression of other angiogenic factors may be upregulated, leading to compensation and limiting the efficacy of anti-VEGF treatment. In addition, many patients with DME do not show complete resolution of edema despite multiple intravitreal injections of anti-VEGF drugs. Moreover, in those patients who respond, the effect might be transient. This underlines the need for additional therapies.
The fact that a substantial proportion of patients fails to respond to anti-VEGF monotherapy suggests that factors other than VEGF may be important in this disease. Therefore, the aims are to broaden general knowledge about DR on the basis of recent laboratory and clinical findings and to identify novel key pathways that drive DR initiation and progression to find innovative therapeutic strategies.
This Research Topic welcomes the submission of manuscripts focusing on, but not limited to, the following areas:
• Identification of additional therapeutic targets, creating the possibility to inhibit different pathways simultaneously
• Targeting novel factors, preferably with VEGF-independent signaling pathways
• Innovative neuroprotective treatment strategies
• Novel drug delivery systems