A combined experimental-computational approach for retinal characterization

Subretinal injection of gene products is the only treatment option for inherited retinal diseases. However, this procedure induces localized high multiaxial deformations, potentially causing irreversible tissue damage due to retinal overstretching and tearing. Comprehensive characterization of retinal mechanical behavior is essential for performing safe injections. Although uniaxial tensile test has been used in the literature, it has many limitations for retinal characterization. To date, retinal mechanical properties are poorly understood due to the lack of standardized testing protocol. This study aimed to introduce a combined experimental-computational approach using small punch testing and finite element simulations to investigate retina elastic behavior under biaxial deformations. To develop a suitable testing protocol for retinal samples, we evaluated the impact of environmental conditions on retinal elasticity by performing uniaxial tensile tests on porcine retinal strips in air, in a saline bath, and at different temperatures. The results showed that conditions did not significantly affect the elastic modulus. We then developed an easy and reproducible small punch test protocol, allowing to measure for the first time the load-displacement response of the retina under biaxial deformations. Computational simulations enabled the analysis of retinal deformations and the identification of its elastic modulus (5.5 kPa). The outcomes of this study highlight the great potential of the combined approach as a viable alternative to uniaxial tensile test to advance the understanding of retinal biomechanics. This is essential not only for minimizing sight-threatening surgical complications during injections, but also for building predictive in silico models, and developing biomimetic scaffolds.