The neuroscience of diabetic retinopathy

Abstract

Diabetic retinopathy remains a leading cause of blindness despite recent advance in therapies. Traditionally, this complication of diabetes was viewed predominantly as a microvascular disease but research has pointed to alterations in ganglion cells, glia, microglia, and photoreceptors as well, often occurring without obvious vascular damage. In neural tissue, the microvasculature and neural tissue form an intimate relationship with the neural tissue providing signaling cues for the vessels to form a distinct barrier that helps to maintain the proper neuronal environment for synaptic signaling. This relationship has been termed the neurovascular unit (NVU). Research is now focused on understanding the cellular and molecular basis of the neurovascular unit and how diabetes alters the normal cellular communications and disrupts the cellular environment contributing to loss of vision in diabetes.

Integrative Biology of Diabetic Retinal Disease: Lessons from Diabetic Kidney Disease

“…Together, these clinical phenotype modalities suggest that at least a subset of persons with diabetes experience visual function loss primarily from neurodegeneration [57][58][59], perhaps independent of the vascular structural abnormalities observed in NPDR (Non-proliferative diabetic retinopathy) and PDR (Proliferative diabetic retinopathy) [60,61]. The relationship between these phenotypes warrants further investigation [62,63]. To this end, visual function testing such as contrast sensitivity and visual fields are secondary endpoints in large clinical trials (NCT04661358 and NCT042655261), and a new DRD grading scale is being developed that will include visual function testing as an integral component [64].…”

The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function

“…These restrict paracellular flux. As with endothelial cells of the BBB [ 47 ], they have few vesicles and no fenestrae formation reducing transcellular permeability [ 48 ]. The cells also express characteristic transporter patterns, amongst them, efflux transporters of the multi-drug resistance family [ 48 , 49 ].…”

“…As with endothelial cells of the BBB [ 47 ], they have few vesicles and no fenestrae formation reducing transcellular permeability [ 48 ]. The cells also express characteristic transporter patterns, amongst them, efflux transporters of the multi-drug resistance family [ 48 , 49 ]. As in the brain, formation of this very tight phenotype requires interaction with tissue-specific neighbouring cells like neurons, glia, and pericytes.…”

“…As in the brain, formation of this very tight phenotype requires interaction with tissue-specific neighbouring cells like neurons, glia, and pericytes. Ultimately, this leads to the concept of the neurovascular unit ( Figure 1 ) [ 48 ]. The glia and pericytes provide endothelial support and maintenance, and as for the BBB, their damage inevitably results in reduced endothelial tightness [ 50 ].…”

Müller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P1 in diabetic retinopathy

“…[3][4][5] However, present treatment, including laser photocoagulation, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs, or vitreoretinal surgery can only restore and maintain part of the vision, making early control of abnormal angiogenesis desperately needed for the treatment of DR. [6][7][8][9] It has long been known that DR is a complex and heterogeneous retinal degenerative disease with all components of the retina being disrupted in disease progression. 10 The term, "neurovascular unit," was first introduced to emphasize the intimate relationship between the brain and its vessels. 11,12 As part of the central nervous system, the retina is composed of neurons, glia cells, endothelial cells, peri-cytes, and extracellular matrix components.…”