The retinal pigment epithelium (RPE) is the outermost cell layer of the retina. It has several important physiological functions, among which is removal of excess fluid from the sub-retinal space by pumping it isotonically towards the choroid. Failure of this pumping leads to fluid accumulation, which is closely associated with several pathological conditions, such as age-related macular degeneration, macular oedema and retinal detachment. In the present work we study mechanisms responsible for fluid transport across the RPE with the aim of understanding how fluid accumulation can be prevented. We focus on two possible mechanisms, osmosis and electroosmosis, and develop a spatially resolved mathematical model that couples fluid and ion transport across the epithelium, accounting for the presence of Na,K and Cl ions. Our model predicts spatial variability of ion concentrations and the electrical potential along the cleft gap between two adjacent cells, which osmotically drives the flow across the lateral membranes. This flow is directed from the sub-retinal space to the choroid and has a magnitude close to measured values. Electroosmosis is subdominant by three orders of magnitude to osmosis and has an opposite direction, suggesting that local osmosis is the main driving mechanism for water transport across the RPE.
The retina is composed of two main layers—the neuroretina and the retinal pigment epithelium (RPE)—that are separated by a potential gap termed the sub-retinal space (SRS). Accumulation of fluid in the SRS may result in a retinal detachment. A key function of the RPE is to prevent fluid accumulation in the SRS by actively pumping fluid from this space to the choroid. We have developed a mathematical model of this process that incorporates the transport of seven chemical species: Na
+
, K
+
, Cl
−
,
HCO3−
, H
+
, CO
2
and H
2
CO
3
. This allows us to estimate solute and water fluxes and to understand the role of the different membrane ion channels. We have performed a global sensitivity analysis using the extended Fourier amplitude sensitivity test to investigate the relative importance of parameters in generating the model outputs. The model predicts that flow across the RPE is driven by an osmotic gradient in the cleft gap between adjacent cells. Moreover, the model estimates how water flux is modified in response to inhibition of membrane ion channels and carbonic anhydrase (CA). It provides a possible explanation for how CA inhibitors, which are used clinically to prevent fluid accumulation in the SRS, may be acting.
Motivated by recent experiments demonstrating that motile algae get trapped in draining foams, we study the trajectories of microorganisms confined in model foam channels (section of a Plateau border). We...
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