Precision Medicines for Retinal Lipid Metabolism-Related Pathologies

Abstract

Oxidation of lipids and lipoproteins contributes to inflammation processes that promote the development of eye diseases. This is a consequence of metabolism dysregulation; for instance, that of the dysfunctional peroxisomal lipid metabolism. Dysfunction of lipid peroxidation is a critical factor in oxidative stress that causes ROS-induced cell damage. Targeting the lipid metabolism to treat ocular diseases is an interesting and effective approach that is now being considered. Indeed, among ocular structures, retina is a fundamental tissue that shows high metabolism. Lipids and glucose are fuel substrates for photoreceptor mitochondria; therefore, retina is rich in lipids, especially phospholipids and cholesterol. The imbalance in cholesterol homeostasis and lipid accumulation in the human Bruch’s membrane are processes related to ocular diseases, such as AMD. In fact, preclinical tests are being performed in mice models with AMD, making this area a promising field. Nanotechnology, on the other hand, offers the opportunity to develop site-specific drug delivery systems to ocular tissues for the treatment of eye diseases. Specially, biodegradable nanoparticles constitute an interesting approach to treating metabolic eye-related pathologies. Among several drug delivery systems, lipid nanoparticles show attractive properties, e.g., no toxicological risk, easy scale-up and increased bioavailability of the loaded active compounds. This review analyses the mechanisms involved in ocular dyslipidemia, as well as their ocular manifestations. Moreover, active compounds as well as drug delivery systems which aim to target retinal lipid metabolism-related diseases are thoroughly discussed.

Age-Related Macular Degeneration and Mitochondria-Associated Autoantibodies: A Review of the Specific Pathogenesis and Therapeutic Strategies

“…Medications targeting lipid metabolism, such as desipramine, docosahexaenoic acid, apolipoprotein mimetics, and statins, are currently being considered as effective treatments for AMD [125]. As mitochondria are involved in cholesterol regulation, one of the therapeutic options for lipid metabolism intervention is to maintain normal lipid oxidation levels in RPE cells by preserving mitochondrial function [126]. In one study, RPE-specific mitochondrial transcription factor A (TFAM)-knockout mice exhibited an increased activation of the mammalian target of rapamycin (mTOR) pathway, which plays an important role in promoting lipid biosynthesis [125,127].…”