Vasoactive neuropeptides in clinical ophthalmology: An association with autoimmune retinopathy?

The mammalian eye is protected against pathogens and inflammation in a relatively immune-privileged environment. Stringent mechanisms are activated that regulate external injury, infection, and autoimmunity. The eye contains a variety of cells expressing vasoactive neuropeptides (VNs), and their receptors, located in the sclera, cornea, iris, ciliary body, ciliary process, and the retina. VNs are important activators of adenylate cyclase, deriving cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Impairment of VN function would arguably impede cAMP production and impede utilization of ATP. Thus VN autoimmunity may be an etiological factor in retinopathy involving perturbations of purinergic signaling. A sound blood supply is necessary for the existence and functional properties of the retina. This paper postulates that impairments in the endothelial barriers and the blood–retinal barrier, as well as certain inflammatory responses, may arise from disruption to VN function. Phosphodiesterase inhibitors and purinergic modulators may have a role in the treatment of postulated VN autoimmune retinopathy

Postulated Role of Vasoactive Neuropeptide-Related Immunopathology of the Blood Brain Barrier and Virchow-Robin Spaces in the Aetiology of Neurological-Related Conditions

Vasoactive neuropeptides (VNs) such as pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) have critical roles as neurotransmitters, vasodilators including perfusion and hypoxia regulators, as well as immune and nociception modulators. They have key roles in blood vessels in the central nervous system (CNS) including maintaining functional integrity of the blood brain barrier (BBB) and blood spinal barrier (BSB). VNs are potent activators of adenylate cyclase and thus also have a key role in cyclic AMP production affecting regulatory T cell and other immune functions. Virchow-Robin spaces (VRSs) are perivascular compartments surrounding small vessels within the CNS and contain VNs. Autoimmunity of VNs or VN receptors may affect BBB and VRS function and, therefore, may contribute to the aetiology of neurological-related conditions including multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. VN autoimmunity will likely affect CNS and immunological homeostasis. Various pharmacological and immunological treatments including phosphodiesterase inhibitors and plasmapheresis may be indicated

γδ T cell response to prolonged heavy endurance exercise

The focus of this study was to assess exercise-induced alterations in circulating γδ T cell subpopulations and memory phenotypes after a prolonged heavy-intensity exercise bout. Ten highly-trained endurance cyclists (mean ± SEM: age 24.0 ± 1.3 years; height 1.81 ± 0.02 m; body mass 73.3 ± 1.8 kg; peak oxygen uptake 60.7 ± 1.5 mL.kg-1.min-1) performed 2 h of cycling exercise at 90% of the second ventilatory threshold. Blood samples were collected before exercise, immediately post-exercise, 1 h, 2 h, 4 h, and 6 h post-exercise. Flow cytometry was used to examine γδ T cell subsets, memory phenotypes and receptor expression. A significant decrease in cell concentration was observed in total γδ T cells and the δ2 subset from pre-exercise to 1 h, 2 h, and 4 h post-exercise. Further analysis of the δ2 subset revealed a significant decrease from pre-exercise to 1 h, 2 h, and 4 h post-exercise in naive δ2 cells, and a significant decrease from pre-exercise to 1 h and 2 h post-exercise in central memory δ2 cells. A significant decrease was observed in γδ T cells expressing CD11ahigh, CD62Lhigh and CD94+ from pre-exercise to 1 h, 2 h, and 4 h post-exercise. Furthermore, a significant decrease was observed from pre-exercise to 1 h post-exercise in CD62Llow and CD94- γδ T cells. These results suggest an exercise-stress-induced redistribution of γδ T cells from the circulation with greater propensity for antigen stimulation, tissue and lymph node homing potential for a duration of 4 h after the cessation of exercise