Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma

Duarte, Joao N.

doi:10.1155/2021/4581909

Cited by 39 publications

(33 citation statements)

References 209 publications

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“…The presence of photoreceptors that are rich in fatty acids makes the retina susceptible to oxidation [19]. In the same way, different pathologies that affect this tissue are closely related to inflammatory processes [20][21][22]. Therefore, many pathologies related to the posterior pole of the eye have been associated with these two processes, sharing their pathophysiology not only in oxidative stress but also in inflammation phenomena.…”

Section: Oxidative Stress and Inflammationmentioning

confidence: 99%

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

et al. 2021

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Most irreversible blindness observed with glaucoma and retina-related ocular diseases, including age-related macular degeneration and diabetic retinopathy, have their origin in the posterior segment of the eye, making their physiopathology both complex and interconnected. In addition to the age factor, these diseases share the same mechanism disorder based essentially on oxidative stress. In this context, the imbalance between the production of reactive oxygen species (ROS) mainly by mitochondria and their elimination by protective mechanisms leads to chronic inflammation. Oxidative stress and inflammation share a close pathophysiological process, appearing simultaneously and suggesting a relationship between both mechanisms. The biochemical end point of these two biological alarming systems is the release of different biomarkers that can be used in the diagnosis. Furthermore, oxidative stress, initiating in the vulnerable tissue of the posterior segment, is closely related to mitochondrial dysfunction, apoptosis, autophagy dysfunction, and inflammation, which are involved in each disease progression. In this review, we have analyzed (1) the oxidative stress and inflammatory processes in the back of the eye, (2) the importance of biomarkers, detected in systemic or ocular fluids, for the diagnosis of eye diseases based on recent studies, and (3) the treatment of posterior ocular diseases, based on long-term clinical studies.

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Section: Oxidative Stress and Inflammationmentioning

confidence: 99%

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

et al. 2021

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“…Amongst all the neuron types, RGCs, due to their morphological features and their high energy requirements, are particularly vulnerable to mitochondrial dysfunction. In fact, a lack of saltatory conduction, due to unmyelinated axons of RGCs within the retina, leads to a higher requirement of more mitochondria in order to respond to the high metabolic demand [ 19 ]. Therefore, to provide RGCs with the correct energy contribution, the mitochondria integrity, in terms of their biogenesis, dynamics, transport and degradation (e.g., mitophagy), is required.…”

Section: Retinal Ganglion Cellsmentioning

confidence: 99%

“…This effect provokes RGC damage exacerbation at a retinal tissue level [ 127 , 128 ]. The increase in Complement activation has been linked to reduced RGC survival both in humans and in animal glaucoma models, suggesting its crucial role in glaucoma progression [ 19 ].…”

Section: Retinal Ganglion Cellsmentioning

confidence: 99%

Risk Factors for Retinal Ganglion Cell Distress in Glaucoma and Neuroprotective Potential Intervention

Vernazza

Oddone

Tirendi

et al. 2021

IJMS

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Retinal ganglion cells (RGCs) are a population of neurons of the central nervous system (CNS) extending with their soma to the inner retina and with their axons to the optic nerve. Glaucoma represents a group of neurodegenerative diseases where the slow progressive death of RGCs results in a permanent loss of vision. To date, although Intra Ocular Pressure (IOP) is considered the main therapeutic target, the precise mechanisms by which RGCs die in glaucoma have not yet been clarified. In fact, Primary Open Angle Glaucoma (POAG), which is the most common glaucoma form, also occurs without elevated IOP. This present review provides a summary of some pathological conditions, i.e., axonal transport blockade, glutamate excitotoxicity and changes in pro-inflammatory cytokines along the RGC projection, all involved in the glaucoma cascade. Moreover, neuro-protective therapeutic approaches, which aim to improve RGC degeneration, have also been taken into consideration.

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“…Damage to mitochondria may accumulate over many years and a functional decline could be caused by blue light-induced damage to mitochondrial proteins [29,30], or accumulating mitochondrial DNA damage [31]. Either of these events will lead to the production of reactive oxygen species by damaged mitochondria that further degrade their function [32].…”

Section: Metabolic and Mitochondrial Rgc Stressmentioning

confidence: 99%

Immune Responses in the Glaucomatous Retina: Regulation and Dynamics

Shestopalov

Spurlock

Gramlich

et al. 2021

Cells

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Glaucoma is a multifactorial disease resulting in progressive vision loss due to retinal ganglion cell (RGC) dysfunction and death. Early events in the pathobiology of the disease include oxidative, metabolic, or mechanical stress that acts upon RGC, causing these to rapidly release danger signals, including extracellular ATP, resulting in micro- and macroglial activation and neuroinflammation. Danger signaling also leads to the formation of inflammasomes in the retina that enable maturation of proinflammatory cytokines such IL-1β and IL-18. Chronic neuroinflammation can have directly damaging effects on RGC, but it also creates a proinflammatory environment and compromises the immune privilege of the retina. In particular, continuous synthesis of proinflammatory mediators such as TNFα, IL-1β, and anaphylatoxins weakens the blood–retina barrier and recruits or activates T-cells. Recent data have demonstrated that adaptive immune responses strongly exacerbate RGC loss in animal models of the disease as T-cells appear to target heat shock proteins displayed on the surface of stressed RGC to cause their apoptotic death. It is possible that dysregulation of these immune responses contributes to the continued loss of RGC in some patients.

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Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma

Cited by 39 publications

References 209 publications

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

Risk Factors for Retinal Ganglion Cell Distress in Glaucoma and Neuroprotective Potential Intervention

Immune Responses in the Glaucomatous Retina: Regulation and Dynamics

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