Department of Civil, Chemical and Environmental Engineering, University of Genoa, Via Montallegro 1, Genoa 16145, Italy.
Department of Ophthalmology, Nottingham University Hospitals NHS Trust, Nottingham NG5 1PB, UK.
J Theor Biol. 2018 Nov 7;456:233-248. doi: 10.1016/j.jtbi.2018.08.009. Epub 2018 Aug 7.
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.
视网膜色素上皮(RPE)是视网膜的最外层细胞层。它具有几种重要的生理功能,其中之一是通过将多余的液体等渗地泵向脉络膜来从视网膜下腔去除液体。这种泵送的失败会导致液体积累,这与几种病理状况密切相关,如年龄相关性黄斑变性、黄斑水肿和视网膜脱离。在本工作中,我们研究了负责 RPE 中液体转运的机制,目的是了解如何防止液体积累。我们专注于两种可能的机制,渗透和电渗,并开发了一个空间分辨的数学模型,该模型耦合了跨上皮的流体和离子运输,考虑了 Na、K 和 Cl 离子的存在。我们的模型预测了离子浓度和电势能沿两个相邻细胞之间的裂隙间隙的空间变化,这会在侧向膜上驱动渗透流。这种流动从视网膜下腔指向脉络膜,并且具有接近测量值的大小。电渗比渗透小三个数量级,并且方向相反,表明局部渗透是 RPE 中跨膜水转运的主要驱动机制。