Abstract
Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina.
Highlights
Diabetic retinopathy, a major complication of diabetic patients, is the leading cause of vision loss worldwide [1]
Since 1998 [5], growing evidence has been demonstrating that neuronal abnormalities including neuronal cell death is related to the pathogenesis of the early stage of diabetic neuropathy in the retina in vitro [6,7,8,9,10,11,12,13,14,15,16], in vivo animal models [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], in human retinas [5,36,37,38], and in clinical studies from the findings of optical coherence tomography in patients with no or minimal diabetic retinopathy [39,40,41,42,43,44,45,46]
Diabetic retinopathy is a highly tissue-specific neurovascular complication of both type 1 and type 2 diabetes, and the impairment of neurovascular unit is associated with the early stages of diabetic retinopathy
Summary
A major complication of diabetic patients, is the leading cause of vision loss worldwide [1]. Since 1998 [5], growing evidence has been demonstrating that neuronal abnormalities including neuronal cell death is related to the pathogenesis of the early stage of diabetic neuropathy in the retina in vitro [6,7,8,9,10,11,12,13,14,15,16], in vivo animal models [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], in human retinas [5,36,37,38], and in clinical studies from the findings of optical coherence tomography in patients with no or minimal diabetic retinopathy [39,40,41,42,43,44,45,46]. This review will be helpful for giving clues to establish regenerative therapies for diabetic neuropathy of the retina
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