**2. Diabetic retinopathy pathophysiology**

Chronic hyperglycemia, hyperlipidemia, and hypertension are involved in the development of DR [5]. Specifically chronic hyperglycemia has been linked to changes within the retinal microvasculature. Chronic hyperglycemia can result in damage through multiple mechanisms including osmotic alterations due to sorbitol accumulation from the polyol pathway, increased nonenzymatic glycosylation of proteins and reactive oxygen species, and activated protein kinase C [6]. These mechanisms contribute to dysfunction of endothelial cells and pericytes, ultimately leading to DR and potentially DME. Endothelial cells support the blood-retinal barrier and pericytes regulate capillary blood flow [7]. Damage to endothelial cells results in fluid accumulation in the macula [4, 8]. Damage to pericytes causes poor regulation of blood flow and microaneurysms within these vessels [9]. Ultimately, microvascular damage of the retina culminates in vision loss due to poor retinal perfusion and ischemia, upregulation of growth factors and inflammatory cytokines, and angiogenesis [6, 10]. Among these growth factors and inflammatory cytokines, VEGF and angiopoietins play important roles and are targets of interest for therapeutic interventions [11].
