Structural and Functional Rescue of Chronic Metabolically Stressed Optic Nerves through Respiration

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Mohammad Harun-Or-RashidDenise M Inman

Abstract

Axon degeneration can arise from metabolic stress, potentially a result of mitochondrial dysfunction or lack of appropriate substrate input. In this study, we investigated whether the metabolic vulnerability observed during optic neuropathy in the DBA/2J (D2) model of glaucoma is due to dysfunctional mitochondria or impaired substrate delivery to axons, the latter based on our observation of significantly decreased glucose and monocarboxylate transporters in D2 optic nerve (ON), human ON, and mice subjected to acute glaucoma injury. We placed both sexes of D2 mice destined to develop glaucoma and mice of a control strain, the DBA/2J-Gpnmb+, on a ketogenic diet to encourage mitochondrial function. Eight weeks of the diet generated mitochondria, improved energy availability by reversing monocarboxylate transporter decline, reduced glial hypertrophy, protected retinal ganglion cells and their axons from degeneration, and maintained physiological signaling to the brain. A robust antioxidant response also accompanied the response to the diet. These results suggest that energy compromise and subsequent axon degeneration in the D2 is due to low substrate availability secondary to transporter downregulation.SIGNIFICANCE STATEMENT We sh...Continue Reading

Citations

Nov 15, 2018·Journal of Neuroinflammation·Mohammad Harun-Or-Rashid, Denise M Inman
Jan 3, 2019·Investigative Ophthalmology & Visual Science·Assraa H Jassim, Denise M Inman
Apr 14, 2019·Molecular Neurobiology·Assraa Hassan JassimDenise M Inman
May 15, 2019·Biology·Janis T Eells
Aug 11, 2019·Scientific Reports·Wendi S LambertDavid J Calkins
Sep 26, 2020·Annals of Biomedical Engineering·Assraa Hassan JassimDenise M Inman
Jan 30, 2021·The Journal of Clinical Endocrinology and Metabolism·Sunder MudaliarDaniel L Chao
Mar 1, 2021·Progress in Retinal and Eye Research·David J Calkins
Jul 28, 2020·Progress in Retinal and Eye Research·Robert J CassonJohn P M Wood
Mar 20, 2021·Antioxidants & Redox Signaling·Assraa Hassan JassimDenise M Inman
Apr 3, 2021·Frontiers in Neurology·Mariana Y García-BermúdezMiriam Kolko
Aug 10, 2021·Frontiers in Pharmacology·Assraa Hassan JassimClaire H Mitchell
Jun 2, 2021·Annual Review of Vision Science·Laura CampelloAnand Swaroop

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.