Malfunction of outer retinal barrier and choroid in the occurrence and progression of diabetic macular edema

Abstract

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, affecting 1 in 15 patients with diabetes mellitus (DM). The disruption of the inner blood-retina barrier (BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris, in the occurrence and evolution of DME. The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition. In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.

Correlation between Choroidal Vascularity Index and Outer Retina in Patients with Diabetic Retinopathy

“…Reduced choroidal thickness associated with DR may lead to the hypoxia of retinal tissues, resultant impairment of outer BRB, development of DME, and further progression thereof [6]. At a molecular level, hyperglycemia is associated with the activation of various pathways, including polyol pathway, protein kinase C pathway, generation of advanced glycation end-products, inflammation, and oxidative stress [24,52]. Activation of those pathways affects retinal and choroidal vessels and neurons, RPE cells, and glial cells [26,53].…”

“…Choroidopathy may trigger the development of retinopathy due to retinal tissue hypoxia and overexpression of vascular endothelial growth factor (VEGF); this contributes to further retinal damage and DME [5,20]. However, it is still unclear whether choroidopathy precedes, accompanies, or follows the retinal changes [3,[22][23][24]. Moreover, the exact contribution of diabetic choroidopathy to the diabetes-associated damage of the neuroretina and occurrence of DME remains poorly understood [22].…”

“…ELM is an intercellular junction between the Müller cells and photoreceptor cells, constituting a barrier for macromolecules [30]; a disruption of ELM may result in the migration of blood components into the outer retinal layers and resultant exacerbation of photoreceptor damage. ELM can be altered due to hyperglycemia [24]. ORL includes outer and inner segments of photoreceptors and RPE.…”

“…RPE constitutes the outer BRB. It removes the waste that remained after the phagocytosis of photoreceptors' outer segments, provides nutrients for photoreceptors, absorbs light, pumps the fluid towards choriocapillaris, and controls retinal oxidative stress [24].…”

“…In the present study, we focused on choroidopathy, a component of DR and DME pathogenesis [3,5,20,[22][23][24]. We aimed to explain the relationship between outer retinal and choroidal parameters.…”