Dynamics of Cyclooxygenase-1 Positive Microglia/Macrophage in the Retina of Pathological Model Mice as a Biomarker of the Retinal Inflammatory Diseases

Abstract

In an intraocular inflammatory state, microglia residing in the retina become active and migrate inside the retina. In this study, we investigated whether cyclooxygenase-1 (COX-1) expressed by retinal microglia/macrophage can be a biomarker for the diagnosis of retinal diseases. COX-1 was immunopositive in microglia/macrophage and neutrophils, while COX-2 was immunopositive in astrocytes and neurons in the inner layer of normal retina. The number of COX-1 positive cells per section of the retinal tissue was 14 ± 2.8 (mean ± standard deviation) in normal mice, which showed significant increase in the lipopolysaccharide (LPS)-administrated model (62 ± 5.0, p = 8.7 × 10−9). In addition to microglia, we found neutrophils that were positive for COX-1. In the early stage of inflammation in the experimental autoimmune uveoretinitis (EAU), COX-1 positive cells, infiltrating from the ciliary body into the retinal outer nuclear layer, were observed. The number of infiltrating COX-1 positive cells correlated with the severity of EAU. Taken together, the increased number of COX-1 positive microglia/macrophage with morphological changes were observed in the retinas of retinal inflammatory disease models. This suggests that COX-1 can be a marker of disease-related activities of microglia/macrophage, which should be useful for the diagnosis of retinal diseases.

Local Myeloid-Derived Suppressor Cells Impair Progression of Experimental Autoimmune Uveitis by Alleviating Oxidative Stress and Inflammation

“… 17 , 44 During oxidative stress and inflammatory responses, macrophages release metabolic products, such as antimicrobial peptides, reactive nitrogen species (NO), and reactive oxygen species, representative of the innate immune mechanism. 17 , 45 The migration of activated microglia and macrophages into the outer retinal layer leads to the secretion of pathogenic factors, such as peroxynitrite and TNF-α. 16 , 46 During early phase innate immune reactions, the release of proinflammatory mediators, including nitrogen oxides, IL-1β, IL-6, TNF-α, and reactive oxygen species, mediate tissue injuries 18 , 47 and play a crucial role as an effector of innate immunity and an amplifier of acquired immunity.…”