New strategies that can be neuroprotective

Abstract

AbstractGlaucoma is considered a neurodegenerative disease and shares some common mechanisms with other neurodegenerative diseases. Therefore, research into the triggers and drivers of neurodegeneration can identify novel areas of therapeutic intervention to preserve and restore vision. Neuroprotection in glaucoma is focused on preserving the neuronal structure and/or function. Currently, lowering of intraocular pressure (IOP) is the only clinically proven neuroprotective strategy. Alternatives to IOP‐lowering approach can be grouped into targets that interfere with excitotoxicity, oxidative stress and mitochondrial dysfunction, inflammation‐abnormal immune response, glial cell modulation, and stem cell therapy. However, any division is arbitrary as most targets are involved in several pathways and/or mechanism of action are incompletely understood. Many agents have shown neuroprotective effect in glaucoma research models but translation into well‐designed human trials and clinical practice represents a major challenge. Several compounds with antioxidant function including vitamin E, C, flavonoids, coenzyme Q10, and citicoline have shown neuroprotective effect in neurodegenerative diseases. Recently, oral nicotinamide supplementation has led to a short‐term improvement of inner retinal function in glaucoma patients. Immune system modulation such as blocking selectively excessive TNF‐alpha and targeting antibodies against ϒ‐Synuclein may prove beneficial. Recently, the receptor agonists of the incretin hormone glucagon‐like‐peptide‐1 (GLP‐1), used for the treatment of diabetes, have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain and the retina. Platelet‐derived growth factor and ciliary neurotrophic factor (CNTF) protect cells from neurodegeneration and phase I studies using intraocular implants with slow CNTF release are ongoing. Intravitreal administration of mesenchymal stromal stem cells has shown neuroprotective effect. Gene therapy in glaucoma is still in preclinical phase. A novel adeno‐associated viral vector gene therapy increased production of brain‐derived neurotrophic factor and its receptor and had neuroprotective effect over several months. Altered levels of microRNAs, small non‐coding RNAs involved in post transcriptional regulation of gene expression, were found to be implicated in retinal ganglion cell apoptosis in glaucoma. MicroRNAs may become a novel neuroprotective strategy.