Animal Models in Eye Research: Focus on Corneal Pathologies.

The eye is a complex sensory organ that enables visual perception of the world. The dysfunction of any of these tissues can impair vision. Conduction studies on laboratory animals are essential to ensure the safety of therapeutic products directly applied or injected into the eye to treat ocular diseases before eventually proceeding to clinical trials. Among these tissues, the cornea has unique homeostatic and regenerative mechanisms for maintaining transparency and refraction of external light, which are essential for vision. However, being the outermost tissue of the eye and directly exposed to the external environment, the cornea is particularly susceptible to injury and diseases. This review highlights the evidence for selecting appropriate animals to better understand and treat corneal diseases, which rank as the fifth leading cause of blindness worldwide. The development of reliable and human-relevant animal models is, therefore, a valuable research tool for understanding and translating fundamental mechanistic findings, as well as for assessing therapeutic potential in humans. First, this review emphasizes the unique characteristics of animal models used in ocular research. Subsequently, it discusses current animal models associated with human corneal pathologies, their utility in understanding ocular disease mechanisms, and their role as translational models for patients.

Parametric Drug Release Optimization of Anti-Inflammatory Drugs by Gold Nanoparticles for Topically Applied Ocular Therapy.

Eye drops represent 90% of all currently used ophthalmic treatments. Only 0.02% of therapeutic molecules contained in eye drops reach the eye anterior chamber despite their high concentration. The tear film efficiently protects the cornea, reducing access to the target. Thereby, the increase in the drug bioavailability and efficiency must come from the mucoadhesion optimization of the drug delivery system. The gold nanoparticles, used as a drug delivery system in this study, already showcased ultrastable and mucoadhesive properties. The goal was to study the gold nanoparticles' ability to release two specific ophthalmic drugs, flurbiprofen and ketorolac. The parameters of interest were those involving the loading conditions, the gold nanoparticles properties, and the release experimental conditions. The drug release was measured using an in vitro model based on dialysis bags coupled with UV-visible spectroscopy. Gold nanoparticles showed an ability to release different molecules, whether hydrophobic or hydrophilic, in passive or active drug release environments. Based on these preliminary results, gold nanoparticles could represent a promising drug delivery system for ketorolac and flurbiprofen when topically applied through eye drops.

Structure of a Parkinson's Disease-Involved α-Synuclein Peptide Is Modulated by Membrane Composition and Physical State.

α-Synuclein (AS), the protein responsible for Parkinson's disease, contains a 12-residue-long sequence, AS71-82, that is thought to play a crucial role in the α-synuclein aggregation process. Neuronal membranes are direct interacting partners of α-synuclein and play a role in fibrillogenesis by providing a charged catalytic surface, notably from anionic phospholipids. However, details are lacking regarding the impact of membrane composition and the driving forces leading to membrane anchorage and peptide structure conversion. To decipher the interplay of α-synuclein with neuronal membranes, the structure of AS71-82 was investigated in the presence of anionic model membranes. Infrared (IR) spectroscopy and solid-state nuclear magnetic resonance data show that AS71-82 adopts a perfectly in-register parallel ß-sheet structure with fibrillar morphology upon interactions with anionic model membranes. IR thermotropism experiments conducted with several membrane compositions revealed that the phospholipids' phase transition induces a rearrangement of the AS71-82 ß-sheet structure. In contrast, membranes are not significantly affected by the presence of AS71-82, which advocates for the amyloid fibrils to lie loosely on the membrane surface. The results bring new arguments for the lipid-sensing capabilities of AS71-82 and revealed its protofibrillar structure. The striking similarities between AS71-82 and α-synuclein make it a potential good aggregation inhibitor upon chemical modifications.