Animal model for metabolomic diffusion studies in the eye

Abstract

AbstractPurpose: To explore the diffusion capacities between the anterior and posterior chambers in an ex vivo pig eye model using a mix of isotope‐labelled acylcarnitines with different physical and chemical properties and targeted analysis using mass spectrometry (MS).Methods: Enucleated pig eyes were injected in the anterior or posterior chamber of the eye with an acylcarnitine mix (FC‐D3, C2‐D3, C3‐D3, C4‐D3, C8‐D3, FC‐D3, C2‐D3, C3‐D3, C4‐D3, C8‐D3 and C16‐D3 – having an increasing hydrophobicity in that order), then samples were collected from each chamber at 3, 6 and 24 h post‐incubation for further targeted analysis using MS.Results: The acylcarintine concentrations of FC‐D3, C2‐D3, C3‐D3, C4‐D3, C8‐D3 in the posterior chamber after injection in the anterior chamber increased with time, with the largest increase in concentration observed from 6 to 24 h of incubation; C12‐D3 and C16‐D3 seemed to deviate from that pattern. The acylcarnitine concentrations in the anterior chamber after injection in the posterior chamber showed significant decrease in FC‐D3, C2‐D3, C3‐D3, C4‐D3, C8‐D3 and C12‐D3 from 3 to 24 h of incubation, while C16‐D3 – a longer chain molecule, showed an increase in its concentration up to 24 h from injection.Conclusion: We hereby show a distinct diffusion pattern of molecules with different hydrophobicity within and between the anterior and posterior chamber. These results can be useful for optimizing choices and design of therapeutic molecules with higher retaining or depot properties into the two chambers of the eye for future treatment purposes.