Figure 1.

Hypothetic cascade of events occurring in the retina during diabetes and leading to the development of DR. Hyperglycemia induces metabolic changes in the retinal milieu, leading to oxidative stress and inflammation. Oxidative and inflammatory processes cause damages to neuron and glial cells both directly and indirectly by inducing alterations in the production and release of neurotrophic factors. As a consequence, neurodegenerative processes are activated. In an attempt to protect themselves, suffering neurons would trigger production and release of VEGF, mainly by Müller cells, that may act as a neuroprotectant, thus counteracting neurodegeneration (blue arrow). However, if in the early phases of DR VEGF may act as a neuroprotective factor, its prolonged release triggers vascular damages (which, in turn, may reinforce in a different fashion inflammation and retinal damage), ultimately leading to new vessel proliferation. If untreated, neurodegenerative and neovascular processes concur to visual dysfunction, finally leading to vision loss.