Elucidation of Pathophysiology and Novel Treatment for Diabetic Macular Edema Derived from the Concept of Neurovascular Unit

The retina transmits light signals to the brain via a complex structure composed of photoreceptor cells, neurons including ganglion cells, glial cells such as astrocytes and Mueller cells, as well as retinal blood vessels that feed the retina. The retina performs such high-level physiological function and maintains homeostasis effectively through interactions among the cells that form the neurovascular units (NVUs). Furthermore, as a component of the blood‒retinal barrier (BRB), the vascular structure of the retina is functionally based on the NVUs, in which the nervous system and the vascular tissues collaborate in a mutually supportive relationship. Retinal neurons such as ganglion cells and amacrine cells are traditionally considered to be involved only in visual function, but multiple functionality of neurons attracted attention lately, and retinal neurons play an important role in the formation and function of retinal blood vessels. In other words, damage to neurons indirectly affects retinal blood vessels. Diabetic macular edema is the leading cause of vision loss in diabetic retinopathy, and this type of edema results in neurological and vascular disorders. In this article, the regulatory mechanism of retinal capillaries in diabetic macular edema is reviewed from the viewpoint of NVU.