Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells

Abstract

The retinal pigmented epithelium (RPE) is composed of retinal pigmented epithelial cells joined by tight junctions and represents the outer blood-retinal barrier (BRB). The inner BRB is made of endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows the osmotic gradient and flows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins, and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy incriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools.

Predicting retinal tissue oxygenation using an image-based theoretical model

“…The composition of the retinal vasculature must be understood to generate an accurate heterogeneous vascular network model in this study. The retina is divided into ten distinct layers [24], of which only three of these layers are vascularized. Blood is supplied to the retina via the central retinal artery, which gives rise to the main branches of the retinal circulation.…”

Decorin Prevents Retinal Pigment Epithelial Barrier Breakdown Under Diabetic Conditions by Suppressing p38 MAPK Activation

“…The outer BRB separates the neural retina from the choroidal vasculature and fulfills multiple roles that are essential for the maintenance of normal physiological processes in the retina, including (1) transporting nutrients, water, and ions; (2) absorbing light energy; (3) phagocytosing shed photoreceptor outer-segment membranes; (4) secreting essential growth factors such as VEGF and pigmented epithelium-derived factor; and (5) maintaining the immune privilege of the eye. 9,10 Diabetes-induced outer BRB dysfunction has been detected in both humans and animals. [11][12][13][14] Breakdown of the outer BRB is increasingly recognized as playing an important role in the development of diabetic retinopathy (DR).…”

Alterations of the outer retina in non‐arteritic anterior ischaemic optic neuropathy detected using spectral‐domain optical coherence tomography

“…). Willermains and colleagues provided an explanation by proposing cellular shrinkage of the retinal pigment epithelium in the presence of retinal oedema in vitro in response to the rupture of the blood–retina barrier and the subsequent hyperosmolar environment as a general mechanism in retinal vascular diseases …”

“…Willermains and colleagues provided an explanation by proposing cellular shrinkage of the retinal pigment epithelium in the presence of retinal oedema in vitro in response to the rupture of the blood-retina barrier and the subsequent hyperosmolar environment as a general mechanism in retinal vascular diseases. 24 In the acute phase of NAION, the macular region displayed no significant changes in retinal layer thickness (data not shown). The retinal oedema apparently primarily affects the peripapillary areas but not the macula.…”