Probes for INS

RESULTS : In rodent eye (both rat and mouse), CFH mRNA is strongly expressed in the retinal pigment epithelium with some expression also found in inner nuclear (INL) and retinal ganglion cell (RGC) layers of the retina. C3 mRNA is expressed mainly in RGC, INL of retina, ciliary body, corneal epithelium with some expression is also found in rodent retinal pigment epithelium layer. However, in human eye, CFH and C3 mRNA are strongly expressed in the choroid. Some expression is also found in RGC, INL layer of retina, ONH, sclera, cornea endothelial and stroma; and ciliary body. There is no C3 or CFH signal detected in RPE cells.

Microglia, the resident immune cells in the retina and nervous system, make irreplaceable contributions to the maintenance of normal homeostasis and immune surveillance of these systems. Recently, great progress has been made in determining the origin, distribution, features and functions of retinal microglia and in identifying their roles in retinal diseases. In the retinal microenvironment, microglia constantly monitor changes in their surroundings and maintain balanced functions by communicating with other retinal cells. When disturbed, activated microglia may kill degenerated neurons and photoreceptors through phagocytosis and exacerbate retinal injury by producing multiple proinflammatory mediators. Numerous animal studies and in situ analyses of human tissue have shown that retinal microglia are involved in multiple retinal diseases. The functions and mechanisms of activated microglia in retinal disorders are gradually being elucidated. Increasing evidence points towards the dual roles of microglia in the retina and they are regulated by many factors. How to inhibit the detrimental effects of microglia and promote beneficial effects are worth studying. This review focuses primarily on the features and functions of microglia and how they participate in retinal diseases based on existing research findings. We also discuss current opinions about microglial transdifferentiation.

The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.