Hydraulic Permeability of Retinal and Subretinal Layers: Experimental Quantification and Computational Modeling

Alterations in retinal tissue permeability are a hallmark of several ocular pathologies, including diabetic retinopathy and age-related macular degeneration. Although permeability plays a crucial role in maintaining retinal homeostasis, previously reported values vary widely due to differences in animal models, tissue preparation, and experimental configurations. In the present study, the hydraulic permeability of porcine retinal and subretinal layers was quantitatively characterized using a custom Ussing chamber, a two-component system for measuring trans-tissue fluid flow, enabling controlled physiological pressures. Tissue isolation was verified by scanning electron microscopy, which allowed identification of the targeted ocular layers based on their characteristic surface morphology. Neuroretina, BrM-choroid, and RPE-BrM-choroid samples were analyzed, and the effect of tissue fixation was systematically evaluated. Additional experiments were performed on fixed retina to investigate the pressure-permeability relationship. To complement the experimental measurements, a COMSOL Multiphysics model of fluid transport across the ocular layers was developed. The model reproduced the experimental configuration and incorporated experimentally determined transport properties together with tissue mechanical properties to (i) evaluate possible setup-induced artefacts, (ii) verify the analytical estimation of RPE permeability, and (iii) investigate the influence of strain-dependent retinal permeability on fluid transport across the tissue complex. Fixation with 4% formalin did not significantly alter retinal permeability while improving measurement reproducibility. The neuroretina exhibited relatively high intrinsic permeability (∼10^-14 m²), consistent with its elevated metabolic demand, whereas the RPE-BrM-Choroid complex displayed markedly lower permeability, (∼10^-17 m²), reflecting the barrier function of the outer blood-retina barrier. Numerical simulations indicated that the overall hydraulic response is dominated by the RPE-BrM-Choroid complex, while retinal strain-dependent permeability had a negligible influence on the predicted fluid transport, despite the dependence of the permeability-strain relationship on the adopted mechanical assumptions. Overall, this study provides an integrated experimental-computational framework for quantifying retinal and ocular tissue permeability. The proposed approach reduces variability associated with previous methodologies and supports the use of the porcine retina as a biologically relevant model for human tissue. These results provide physiologically relevant parameters for investigating fluid regulation, blood-retina barrier dysfunction, and ocular drug transport.