Peroxide-cyclooxygenase interactions in postasphyxial changes in retinal and choroidal hemodynamics

Area of Science:

• Ophthalmology
• Neonatal Physiology
• Biomedical Science

Background:

• Asphyxia can cause significant hemodynamic changes in the retina and choroid.
• Reactive oxygen species (ROS) and cyclooxygenase (COX) products are implicated in vascular responses to oxidative stress.

Purpose of the Study:

• To investigate the roles of ROS and COX products in retinal and choroidal blood flow alterations following asphyxia in neonatal pigs.
• To explore the relationship between oxidative stress markers, prostanoids, and ocular vasoconstriction.

Main Methods:

• Neonatal pigs were subjected to asphyxia and treated with saline, free radical scavengers, COX inhibitors, or a thromboxane synthase blocker.
• Retinal blood flow (RBF), choroidal blood flow (ChBF), malondialdehyde (MDA), prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) were measured.
• Isolated eyecup preparations were used to assess the constrictive effects of hydrogen peroxide (H2O2) and cumene hydroperoxide on retinal arteries.

Main Results:

• Asphyxia initially increased RBF and ChBF, followed by a decrease at 60 minutes. COX inhibitors and free radical scavengers partially attenuated the initial increase and prevented the later decrease.
• MDA, TxB2, PGE2, and 6-keto-PGF1 alpha levels rose post-asphyxia. COX inhibition reduced MDA, while free radical scavengers reduced prostanoid levels.
• ROS induced retinal artery constriction, which was inhibited by COX and thromboxane synthase inhibitors.

Conclusions:

• Oxidative stress during asphyxia involves ROS generated via the COX pathway, which in turn stimulates thromboxane synthesis.
• Thromboxane mediates oxidative stress-induced ocular vasoconstriction, a potential trigger for neovascularization in retinopathy of prematurity.