Preventing diabetic retinopathy by mitigating subretinal space oxidative stress in vivo

Patients with diabetes continue to suffer from impaired visual performance before the appearance of overt damage to the retinal microvasculature and later sight-threatening complications. This diabetic retinopathy (DR) has long been thought to start with endothelial cell oxidative stress. Yet newer data surprisingly finds that the avascular outer retina is the primary site of oxidative stress before microvascular histopathology in experimental DR. Importantly, correcting this early oxidative stress is sufficient to restore vision and mitigate the histopathology in diabetic models. However, translating these promising results into the clinic has been stymied by an absence of methods that can measure and optimize anti-oxidant treatment efficacy in vivo. Here, we review imaging approaches that address this problem. In particular, diabetes-induced oxidative stress impairs dark-light regulation of subretinal space hydration, which regulates the distribution of interphotoreceptor binding protein (IRBP). IRBP is a vision-critical, anti-oxidant, lipid transporter, and pro-survival factor. We show how optical coherence tomography can measure subretinal space oxidative stress thus setting the stage for personalizing anti-oxidant treatment and prevention of impactful declines and loss of vision in patients with diabetes.