Oxidative stress increases in retinas of dogs in acute glaucoma but not in chronic glaucoma

Abstract

Immunohistochemical staining revealed an increase in markers of oxidative stress and loss of glutathione in neurons with minimal damage during acute glaucoma. Oxidative changes were no longer present in chronic glaucomatous retinas, suggesting transient oxidative stress occurs early in glaucoma. The loss of glutathione in minimally damaged regions occurred without a significant redistribution of glutamate, suggesting oxidative stress may occur before glutamate redistribution. Alteration in markers of oxidative stress occurs early in canine glaucoma, suggesting oxidative stress may contribute to subsequent glutamate redistribution and other damaging processes.

Definition, Classification, and Pathophysiology of Canine Glaucoma

“…12 Other markers for oxidative stress are also increased in the early stages of PACG in dogs. 121 In addition, and perhaps most significantly, oxidative stress is also able to stimulate an immune reaction, activating glial cells or macrophages, upregulating the expression of tumor necrosis factor alpha (TNFa), and increasing the antigen-presenting abilities of resident cells. 118 …”

Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary F2‐ Isoprostanes as Markers of Oxidative Stress in Anemic Dogs

“…O xidative stress results from a variety of inflamma tory and metabolic conditions and has been well documented as a contributor to disease in both the human and veterinary literature. [1][2][3][4][5][6][7][8][9][10][11][12] Oxidative stress is characterized by the production of reactive oxygen species (ROS) that cause cellular injury through direct and indirect mechanisms. Erythrocytes especially are at risk, because of their ubiquity, fragile phospholipid membrane, oxygen and iron content, and unique redox metabolic processes.…”

Genetic and Biochemical Biomarkers in Canine Glaucoma

“…11,22 Immunolabeling for malondialdehyde (MDA) and nitrotyrosine (NT), markers of free radical formation and oxidative stress, was identified in acutely but not chronically glaucomatous retinas. 23 While the location of the highest level of immunostaining for NT was not described, the highest levels for MDA were seen in the nuclei of neurons, including RGCs, photoreceptors of the outer nuclear layer (ONL), and putative neurons of the inner nuclear layer (INL), suggesting an increase in oxidative stress in these cells.…”

“…7,45,83 It is likely important in the retinal damage that occurs in glaucoma, 12,28,50,91 with an apparent transient nature of the oxidative stress suggested, and may affect endothelial cell function. 22,23,63 Neurons, especially RGCs, are particularly sensitive to oxidative stress in glaucoma, which results in reduced levels of antioxidants within the neurons. 11,22 Immunolabeling for malondialdehyde (MDA) and nitrotyrosine (NT), markers of free radical formation and oxidative stress, was identified in acutely but not chronically glaucomatous retinas.…”

“…While an elevated intraocular pressure (IOP) is considered a constant risk factor in canine glaucoma 74 and a major risk factor in human glaucoma, the need for therapeutic interventions that address factors other than IOP is supported by the presence of normal-tension glaucoma and intraocular hypertension without glaucoma in humans, as well as the progression of glaucomatous optic nerve damage and vision loss despite an IOP within the normal range. Other proposed mechanisms involved in glaucoma include neuroinflammation, 59 hypoxia/ischemia, 8,84 increased extracellular glutamate and excitotoxicity, 21 oxidative stress, 23 obstruction of axoplasmic flow, 9 and deprivation of trophic factors. 77 By identifying accurate biomarkers of these processes in the canine glaucoma patient, the stage of disease or effect of an intervention might be more precisely identified.…”