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Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects.

ABSTRACT: BACKGROUND:Retinal ganglion cell (RGC) degeneration is a major feature of glaucoma pathology. Neuroprotective approaches that delay or halt the progression of RGC loss are needed to prevent vision loss which can occur even after conventional medical or surgical treatments to lower intraocular pressure. OBJECTIVE:The aim of this review was to examine the progress in genetics and cellular mechanisms associated with endoplasmic reticulum (ER) stress, RGC dysfunction and cell death pathways in glaucoma. MATERIALS AND METHODS:Here, we review the involvement of neurotrophins like brain derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin receptor kinase (TrkB) in glaucoma. The role of ER stress markers in human and animal retinas in health and disease conditions is also discussed. Further, we analysed the literature highlighting genetic linkage in the context of primary open angle glaucoma and suggested mechanistic insights into potential therapeutic options relevant to glaucoma management. RESULTS:The literature review of the neurobiology underlying neurotrophin pathways, ER stress and gene associations provide critical insights into association of RGCs death in glaucoma. Alteration in signalling pathway is associated with increased risk of misfolded protein aggregation in ER promoting RGC apoptosis. Several genes that are linked with neurotrophin signalling pathways have been reported to be associated with glaucoma pathology. CONCLUSION:Understanding genetic heterogeneity and involvement of neurotrophin biology in glaucoma could help to understand the complex pathophysiology of glaucoma. Identification of novel molecular targets will be critical for drug development and provide neuroprotection to the RGCs and optic nerve.

SUBMITTER: Chitranshi N

PROVIDER: S-EPMC6120108 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects.

Chitranshi Nitin N Dheer Yogita Y Abbasi Mojdeh M You Yuyi Y Graham Stuart L SL Gupta Vivek V

Current neuropharmacology 20180101 7

<h4>Background</h4>Retinal ganglion cell (RGC) degeneration is a major feature of glaucoma pathology. Neuroprotective approaches that delay or halt the progression of RGC loss are needed to prevent vision loss which can occur even after conventional medical or surgical treatments to lower intraocular pressure.<h4>Objective</h4>The aim of this review was to examine the progress in genetics and cellular mechanisms associated with endoplasmic reticulum (ER) stress, RGC dysfunction and cell death pa ...[more]

PMID: 29676228

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Project description:Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes, the mitochondria are required for multiple pivotal processes that include the production of biological energy, the biosynthesis of reactive oxygen species, the control of calcium homeostasis, and the triggering of cell death. The disruption of anyone of these processes has been shown to impact strongly the function of all cells, but especially of neurons. In this review, we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis, Parkinson's disease and Alzheimer's disease. We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle: fusion, fission, production of reactive oxygen species and energy failure. Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes. Therefore, in order to get in depth insights into their health status in neurodegenerative diseases, we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes. Current techniques include Mitostress, Mitotracker, transmission electron microscopy, oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health. We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction. These include canonical drugs, natural compounds, supplements, lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy. In conclusion, because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases, it is critical to develop novel methods to measure the mitochondrial state, and novel therapeutic strategies aimed at improving their health.

Dataset Information

Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects.

Publications

Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects.

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