SPP2127 Seed

The Outer Limiting Membrane: a multimodal approach to investigate an overlooked retinal barrier

01/01/2024 to 31/12/2025

The Outer Limiting Membrane (OLM) is where photoreceptor cells and Müller glia cells bridge, to form a continuous band that supports structurally the photoreceptors at the outer nuclear layer (ONL). The OLM is important for the overall health of the retina serving as a semipermeable barrier. If the integrity of this structure is compromised, this might lead to the progression of retinal dystrophies, caused for example by mutations in Crumbs homologue 1 (CRB1). So far, the profile of the OLM has been under investigated. By assessing the histological profile of different proteins that make up the OLM, we aim to analyze their distribution and the overall spatial composition of this structure in a murine and porcine animal model as well as an iPSC-based model. The functionality of the OLM and the contribution of different cell types will be studied using a Dextran-based assay. In addition, we aim to define the protein-protein interaction landscape of the OLM by combining Laser-Capture Microdissection (LCM) and Mass Spectrometry (MS). Data obtained in this project will provide the first extensive characterization of the baseline parameters of the OLM in multiple models, which will serve as a reference to describe possible alterations in retinal diseases and requirements for therapeutic approaches