Cellular targets in diabetic retinopathy therapy.

Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.

Oxidative Stress and Microvascular Alterations in Diabetic Retinopathy: Future Therapies.

Diabetes is a disease that can be treated with oral antidiabetic agents and/or insulin. However, patients' metabolic control is inadequate in a high percentage of them and a major cause of chronic diseases like diabetic retinopathy. Approximately 15% of patients have some degree of diabetic retinopathy when diabetes is first diagnosed, and most will have developed this microvascular complication after 20 years. Early diagnosis of the disease is the best tool to prevent or delay vision loss and reduce the involved costs. However, diabetic retinopathy is an asymptomatic disease and its development to advanced stages reduces the effectiveness of treatments. Today, the recommended treatment for severe nonproliferative and proliferative diabetic retinopathy is photocoagulation with an argon laser and intravitreal injections of anti-VEGF associated with, or not, focal laser for diabetic macular oedema. The use of these therapeutic approaches is severely limited, such as uncomfortable administration for patients, long-term side effects, the costs they incur, and the therapeutic effectiveness of the employed management protocols. Hence, diabetic retinopathy is the widespread diabetic eye disease and a leading cause of blindness in adults in developed countries. The growing interest in using polyphenols, e.g., resveratrol, in treatments related to oxidative stress diseases has spread to diabetic retinopathy. This review focuses on analysing the sources and effects of oxidative stress and inflammation on vascular alterations and diabetic retinopathy development. Furthermore, current and antioxidant therapies, together with new molecular targets, are postulated for diabetic retinopathy treatment.

Pterostilbene Prevents Early Diabetic Retinopathy Alterations in a Rabbit Experimental Model.

Oxidative stress generated by diabetes plays a key role in the development of diabetic retinopathy (DR), a common diabetic complication. DR remains asymptomatic until it reaches advanced stages, which complicate its treatment. Although it is known that good metabolic control is essential for preventing DR, knowledge of the disease is incomplete and an effective treatment with no side effects is lacking. Pterostilbene (Pter), a natural stilbene with good antioxidant activity, has proved to beneficially affect different pathologies, including diabetes. Therefore, our study aimed to analyse the protective and/or therapeutic capacity of Pter against oxidant damage by characterising early retinal alterations induced by hyperglycaemia, and its possible mechanism of action in a rabbit model of type 1 diabetes mellitus. Pter reduced lipid and protein oxidative damage, and recovered redox status and the main activities of antioxidant enzymes. Moreover, the redox regulation by Pter was associated with activation of the PI3K/AKT/GSK3ß/NRF2 pathway. Our results show that Pter is a powerful protective agent that may delay early DR development.