- Environmental oxidative stress such as air pollution or light-induced oxidative stress are negative factors that promote retinal cell damage and/or death. 

- Intrinsic response to oxidative stress which is mainly caused by: I) inflammation and glyosis, II) endoplasmic reticulum stress and, III) high metabolic rate of the retina.

Oxidative stress impacts on autophagy and mitophagy, increases retinal lipid peroxidation, and induces DNA damage and mutations, being considered a pathological environmental trigger of prevalent multifactorial visual disorders, such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinal inflammation. On the other hand, pathogenic genetic mutations on genes involved in oxidative stress response and cell protection are causative of rare retinal diseases, such as retinitis pigmentosa (RP) and Leber hereditary optic neuropathy (LHON). Therefore, oxidative stress caused by exogenous noxious stimuli and/or misfunction of endogenous protective pathways contribute to inherited retinal dystrophies and leads to an accelerated progression of retinal neurodegeneration. 

As the source and impact of ROS are different depending on the pathology, finding new therapies to avoid damaging ROS formation will be a step forward on preventing or slowing down the progression of these highly incapacitating blinding diseases, whether prevalent or rare. The strategies could be either to enhance the production of antioxidant enzymes, to reduce ROS, or to promote cytoprotective signaling pathways. As a complementary therapy, nutritional changes and diet supplementation with antioxidant properties may have protective effects on ROS produced in the progression of some retinal diseases, depending on the altered signaling pathway.

To sum up, oxidative stress by exogenous or endogenous agents damage the retina and the RPE, triggering apoptosis of photoreceptors and retinal ganglion cells. In prevalent diseases, such as AMD, glaucoma, and diabetic retinopathy, oxidative stress is a trigger of the pathologies, worsening the physiology of retinal cells and accelerating the progression of the disease. In rare genetic disorders, mutations in several causative genes cause metabolic distress and decrease cell resilience to oxidative stress, adding to the progressive attrition of photoreceptors and RGCs, eventually leading to blindness. We hypothesize that other IRD causative genes related to oxidative stress sensing and oxidative stress management, such as genes implicated in the control of autophagy, stress granule formation, or mitochondrial dynamics, will be identified in the near future, widening the landscape of genes and mutations that cause visual disorders. In addition to the more conventional gene therapy tailored to treat specific genetic defects, treatments addressed to increase cytoprotective signaling pathways in front of oxidative stress and to promote retinal cell resilience will provide new avenues to halt the progression of these blinding diseases and restore retinal homeostasis.