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Review
.2020 Apr 23;9(4):347.
doi: 10.3390/antiox9040347.

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

Affiliations
Review

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

Elena B Domènech et al. Antioxidants (Basel)..

Abstract

Retinal cell survival requires an equilibrium between oxygen, reactive oxygen species, and antioxidant molecules that counteract oxidative stress damage. Oxidative stress alters cell homeostasis and elicits a protective cell response, which is most relevant in photoreceptors and retinal ganglion cells, neurons with a high metabolic rate that are continuously subject to light/oxidative stress insults. We analyze how the alteration of cellular endogenous pathways for protection against oxidative stress leads to retinal dysfunction in prevalent (age-related macular degeneration, glaucoma) as well as in rare genetic visual disorders (Retinitis pigmentosa, Leber hereditary optic neuropathy). We also highlight some of the key molecular actors and discuss potential therapies using antioxidants agents, modulators of gene expression and inducers of cytoprotective signaling pathways to treat damaging oxidative stress effects and ameliorate severe phenotypic symptoms in multifactorial and rare retinal dystrophies.

Keywords: age-related macular degeneration (AMD); glaucoma; leber hereditary optic neuropathy (LHON); oxidative stress damage; oxidative stress response; photoreceptors; retina; retinitis pigmentosa.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Oxidative stress agents generate Reactive Oxygen Species (ROS), which are counteracted by antioxidant enzymes. An excess of oxidative stress leads to cellular damage, which can trigger pathways for either cell survival or cell death.
Figure 2
Figure 2
Translational start in presence or absence of cellular stress. In normal conditions and in absence of stress (green arrow pathway), eIF2B catalyzes the exchange of GDP to GTP and allows the coupling of the ternary complex to the 48S complex. The ribosomal subunit 60S can join the complex and the addition of more ribosomes to this complex make a polysome, which is able to translate the mRNA. Upon cellular stress (red arrow pathway), eIF2α is phosphorylated by stress sensor kinases and inhibits eIF2B, precluding the binding to EIF5. The ternary complex generates a 48S* complex instead, which is deficient in eIF2/eIF5 and unable to start the translation. This complex recruits TIA-1 and TIAR proteins to form the SGs. Additionally, SGs recruit more RNA binding proteins, such as PABP. mRNAs move in and out of SGs depending on the cellular translational requirements. Thus, SGs are highly dynamic complexes, in equilibrium with polysomes.
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