Abstract
Diabetic retinopathy is the leading cause of blindness in working age in US and worldwide. Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) are known to be essential for growth, differentiation and survival of neurons in the developing and mature retina. Nevertheless, a growing body of evidence supports an emerging role of neurotrophins in retinal diseases and in particular, diabetic retinopathy. Neurotrophins are initially synthesized in a pro-form and undergo proteolytic cleavage to produce the mature form that activates two distinctive receptors, the tyrosine kinase tropomycin receptor (Trk) and, to lesser extent, the common low affinity p75 neurotrophin receptor (p75NTR). Despite tight glycemic and metabolic control, many diabetic patients continue to experience progressive retinal damage. Understanding the molecular events involved in diabetic retinopathy is extremely important to identify novel therapeutic strategies to halt the disease progression. Diabetes induces imbalance in neurotrophins by increasing its proform, which is associated with upregulation of the p75NTR receptor in the retina. A growing body of evidence supports a link between the imbalance of pro-neurotrophins and early retinal inflammation, neuro-and microvascular degeneration. Therefore, examining changes in the levels of neurotrophins and its receptors might provide a therapeutically beneficial target to combat disease progression in diabetic patients. This commentary aims to highlight the impact of diabetes-impaired balance of neurotrophins and in particular, the NGF and its receptors; TrkA and p75NTR in the pathology of DR.
Highlights
Diabetic retinopathy is the leading cause of blindness in working age in US and worldwide
Earlier work by Hammes et al 1995 showed that treatment of diabetic rats with nerve growth factor (NGF) prevented early retinal ganglion death, Muller cell activation and development of acellular occluded capillaries [7], suggesting the involvement of NGF and other neurotrophins in pathophysiology of Diabetic retinopathy (DR)
There are four types of neurotrophins that have been characterized in mammals including NGF, Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) [9,10,11]
Summary
Diabetic retinopathy (DR) is a severe sight threatening complication of diabetes mellitus and the leading cause of blindness in the worldwide. The retina is a typical neurovascular system with a delicate organization of neurons, glia cells and blood vessels. The inner blood-retina barrier (BRB) is located within endothelium of capillaries and interconnected by the processes of glia (astrocytes and Müller cells) as well as patches of pericytes [3]. Breakdown of BRB as well as leaky blood vessels arising from late neovascularization can cause macular edema and vision loss [4]. Earlier work by Hammes et al 1995 showed that treatment of diabetic rats with nerve growth factor (NGF) prevented early retinal ganglion death, Muller cell activation and development of acellular occluded capillaries [7], suggesting the involvement of NGF and other neurotrophins in pathophysiology of DR.
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