Potential Interplay between Hyperosmolarity and Inflammation on Retinal Pigmented Epithelium in Pathogenesis of Diabetic Retinopathy

Abstract

Diabetic retinopathy is a frequent eyesight threatening complication of type 1 and type 2 diabetes. Under physiological conditions, the inner and the outer blood-retinal barriers protect the retina by regulating ion, protein, and water flux into and out of the retina. During diabetic retinopathy, many factors, including inflammation, contribute to the rupture of the inner and/or the outer blood-retinal barrier. This rupture leads the development of macular edema, a foremost cause of sight loss among diabetic patients. Under these conditions, it has been speculated that retinal pigmented epithelial cells, that constitute the outer blood-retinal barrier, may be subjected to hyperosmolar stress resulting from different mechanisms. Herein, we review the possible origins and consequences of hyperosmolar stress on retinal pigmented epithelial cells during diabetic retinopathy, with a special focus on the intimate interplay between inflammation and hyperosmolar stress, as well as the current and forthcoming new pharmacotherapies for the treatment of such condition.

Retracted Article: Sauchinone inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells

“…4,5 Retina is a highly specialized tissue that is normally protected by the inner and outer blood-retinal barriers. 6 The retinal pigment epithelial (RPE) cells are a group of cells of retinal pigmented epithelium that constitute the outer blood-retinal barrier. In diabetic patients, RPE cells are easily subjected to high glucose (HG)-induced oxidative stress, which nally lead to cell apoptosis.…”

“…4,6 These pathological changes contribute to the rupture of the blood-retinal barrier, which promotes the development of macular edema, the foremost symptom of DR, resulting in sight loss among diabetic patients. 6 Herein, attenuating the HG-induced oxidative stress and cell apoptosis in RPE cells may become a new pharmacotherapy for the treatment of DR. 4 Sauchinone, one of the active lignan isolated from Saururus chinensis, was reported to possess broad bioactivities, such as anti-inammatory, anti-oxidant, anti-tumor, anti-apoptosis and anti-obesity effects. [7][8][9][10] For example, sauchinone protected against oxidative stress-induced skeletal muscle myoblast damage.…”

TRPV4 inhibition prevents increased water diffusion and blood-retina barrier breakdown in the retina of streptozotocin-induced diabetic mice

“…Intracellular swelling may cause reduced water mobility. In this sense, TRPV4 mediates regulatory volume decrease - i.e., decrease in swelling in the presence of sustained hypotonic stress (Hoshi et al, 2018; Willermain et al, 2018)- by transducing increases in Müller cell (Jo et al, 2015) and retinal neuron (Ryskamp et al, 2014) volumes into Ca 2+ signals. However, hematosin-eosin staining suggests greater packing density in Trpv4 −/− retinas compared to wild-type ones.…”

“…Cell loss, OLM disruption, and deregulation of transporters and ion/water channels contribute to BRB breakdown and reduced drainage in DME. These pathological mechanisms are a consequence of fundamental pathways activated by chronic hyperglycemia, including inflammatory ones (Daruich et al, 2018; Klaassen et al, 2013; Willermain et al, 2018).…”

Diabetic Retinopathy and Ocular Melanoma: How Far We Are?

“…The eye is the organ responsible for vision and is anatomically composed of the cornea, iris, crystalline lens, vitreous body and retina [1]. Retina is a metabolically active tissue, transforming the light energy in electrical impulses, forwarding it to the brain through the optic nerve and allowing vision [2,3]. Internal and external retinal blood barriers (BRB) preserve the retina and, under ideal physiological conditions, regulate the flow of ions, proteins and water [3].…”