Oxidative stress in the brain and retina after traumatic injury

Abstract

The brain and the retina share many physiological similarities, which allows the retina to serve as a model of CNS disease and disorder. In instances of trauma, the eye can even indicate damage to the brain via abnormalities observed such as irregularities in pupillary reflexes in suspected traumatic brain injury (TBI) patients. Elevation of reactive oxygen species (ROS) has been observed in neurodegenerative disorders and in both traumatic optic neuropathy (TON) and in TBI. In a healthy system, ROS play a pivotal role in cellular communication, but in neurodegenerative diseases and post-trauma instances, ROS elevation can exacerbate neurodegeneration in both the brain and the retina. Increased ROS can overwhelm the inherent antioxidant systems which are regulated via mitochondrial processes. The overabundance of ROS can lead to protein, DNA, and other forms of cellular damage which ultimately result in apoptosis. Even though elevated ROS have been observed to be a major cause in the neurodegeneration observed after TON and TBI, many antioxidants therapeutic strategies fail. In order to understand why these therapeutic approaches fail further research into the direct injury cascades must be conducted. Additional therapeutic approaches such as therapeutics capable of anti-inflammatory properties and suppression of other neurodegenerative processes may be needed for the treatment of TON, TBI, and neurodegenerative diseases.

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…The pathomechanisms potentially involved in RGC death include the disruption of the blood-brain barrier, leading to the infiltration of activated immune cells such as macrophages and neutrophils. These immune cells produce a significant amount of reactive oxygen species (ROS) and cytokines, further activating microglia and causing damage to mitochondria and endoplasmic reticulum [475][476][477]. Numerous studies on murine and rodent models of TON have demonstrated an overproduction of ROS [478][479][480], as well as a decrease in the antioxidant activity of SOD [478], and CAT [481,482].…”

“…Taken together, many publications gathered evidence on promising preclinical results in animal models of optic nerve trauma. However, an important factor to be considered for practical uses of antioxidants after optic nerve trauma in humans is the prompt administration of the drug after diagnosis [475]. A delay in this context may equivale to unsuccessful effect of the medication, due to early activation of intracellular downstream transductions [475].…”

“…However, an important factor to be considered for practical uses of antioxidants after optic nerve trauma in humans is the prompt administration of the drug after diagnosis [475]. A delay in this context may equivale to unsuccessful effect of the medication, due to early activation of intracellular downstream transductions [475]. Thus, a combination of antioxidants and other medications with possibly different targets, may enhance the probability of effectiveness in contrasting damages after optic nerve injuries [475].…”

“…A delay in this context may equivale to unsuccessful effect of the medication, due to early activation of intracellular downstream transductions [475]. Thus, a combination of antioxidants and other medications with possibly different targets, may enhance the probability of effectiveness in contrasting damages after optic nerve injuries [475].…”

Type I Collagen‐Adhesive and ROS‐Scavenging Nanoreactors Enhanced Retinal Ganglion Cell Survival in an Experimental Optic Nerve Crush Model

“…[ 9 ] To date, the exact mechanism of secondary degeneration is not fully understood, but it is believed to involve complex interactions between inflammation, oxidative stress, and cell apoptosis. In recent years, increasing evidence has suggested that RGC damage is dependent on the imbalanced production and elimination of reactive oxygen species (ROS), [ 1,10–12 ] mainly hydrogen peroxide (H 2 O 2 ), hydroxyl radical (•OH), singlet oxygen ( 1 O 2 ), and superoxide anions (O 2 •− ). [ 13,14 ] In addition, reactive nitrogen species (RNS), especially nitric oxide (NO), can react with the free radical superoxide and contribute to neuronal cell damage in the retina.…”