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. (Invest Ophthalmol Vis Sci.

Summarising the retinal vascular calibres in healthy, diabetic and diabetic retinopathy eyes

“…As mentioned previously, numerous studies have shown that the retinal vasculature changes during the progression of diabetes and DR [8,29,30,31,32].Therefore, in order to improve the accuracy of the estimation of the trunk for both arteries and veins, different data for healthy, diabetics with no-DR and DR subjects were used. All of the individuals in the diabetic and DR groups had no history of hypertension or any other cardiovascular disease.…”

“…In diabetes and DR especially, changes have been identified both in the blood flow and the vessel wall structure, leading to geometric alterations, which can be measured in fundus images [5,6,7,8]. According to the World Health Organization, the global prevalence of diabetes is estimated to be 9% among adults aged 18+ years.…”

Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

“…Compelling evidence indicates that apoptosis is instrumental in glaucoma, retinitis pigmentosa, cataract, retinoblastoma, retinal ischemia, diabetic retinopathy and several eye infections caused by viruses, bacteria, fungi and some protozoans (Kaneda et al 1999;Vemuganti et al 2004;Cottet and Schorderet 2009;Zhang et al 2010;Poznic M 2009;Barber et al 2011;Pinazo-Durán et al 2013). In contrast, we are just beginning to understand the role of autophagy in ocular diseases.…”

Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

“…Some cases report a more dramatic increase in apoptosis, and one study reported a dramatic loss of the photoreceptors after 24 weeks of streptozotocin-diabetes [15], but this result has not been confirmed and is unlikely to model the clinical condition. In contrast, a study on diabetic mice yielded negative findings on apoptosis and loss of neurons [16], but for the most part the consensus appears to be that experimental diabetes in rodents leads to neuronal apoptosis, loss of retinal ganglion cells and reduction in the thickness of the inner retina [17,18].…”