The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy

Abstract

The most striking features of diabetic retinopathy are the vascular abnormalities that are apparent by fundus examination. There is also strong evidence that diabetes causes apoptosis of neural and vascular cells in the retina. Thus, there is good reason to define diabetic retinopathy as a form of chronic neurovascular degeneration. In keeping with the gradual onset of retinopathy in humans, the rate of cell loss in the animal models is insidious, even in uncontrolled diabetes. This is not surprising given that a sustained high rate of cell loss without regeneration would soon lead to catastrophic tissue destruction. The consequences of ongoing cell death are difficult to detect, and even the quantification of cumulative cell loss requires painstaking histology and microscopy. This subtle cell loss raises the issue of the relevance of the phenomenon to the progression of diabetic retinopathy and the ultimate loss of vision. Neuronal function may be compromised in advance of apoptosis, contributing to an early deterioration of vision. Here we review some of the evidence supporting apoptotic cell death as a contributing mechanism of diabetic retinopathy, explore some of the potential causes, and discuss the potential links between apoptosis and loss of visual function in diabetic retinopathy.

Figure 1.

Summary of potential causes of apoptosis in diabetic retinopathy. Evidence from animal models and postmortem human tissue support an increase in apoptosis in the retinal vasculature (left) and neural cells (including all neurons and photoreceptors; right). Some potential mechanisms considered in this Perspective include general ones such as oxidative stress and reduced growth factor signaling, which could induce cell death in all cells. Also considered are glutamate excitotoxicity, which is known to cause apoptosis in neurons though its potential to kill vascular cells is less clear, and neuroinflammation, which is known to induce vascular permeability and may also cause dysfunction in neural tissue.