Assessment of outer retinal thickness and function in mice after experimental optic nerve trauma.

BACKGROUND: Optic nerve trauma caused by crush injury is frequently used for investigating experimental treatments that protect retinal ganglion cells (RGCs) and induce axonal regrowth. Retaining outer retinal light responses is essential for therapeutic rescue of RGCs after injury. However, whether optic nerve crush also damages the structure or function of photoreceptors has not been systematically investigated. In this study, we investigated whether outer retinal thickness and visual function are altered by optic nerve crush in the mouse. METHODS: Wildtype mice underwent optic nerve crush and intravitreal injection of a control solution in one eye with the fellow eye remaining uninjured. Two weeks after injury, the thickness of the ganglion cell region (GCL to IPL) and photoreceptor layer (bottom of the OPL to top of the RPE) were measured using OCT. Retinal function was assessed using flash ERGs. Immunodetection of RGCs was performed on retinal cryosections and RGCs and ONL nuclei rows were counted. Multiple comparison analyses were conducted using Analysis of Variance (ANOVA) with Tukey's post hoc test and P values less than 0.05 were considered statistically significant. RESULTS: Optic nerve crush injury induced RGC death as expected, demonstrated by thinning of the ganglion cell region and RGC loss. In contrast, outer retinal thickness, photopic and scotopic a-wave and b-wave amplitudes and photoreceptor nuclei counts, were equivalent between injured and uninjured eyes. CONCLUSIONS: Secondary degeneration of the outer retina was not detected after optic nerve injury in the presence of significant RGC death, suggesting that the retina has the capacity to compartmentalize damage. These findings also indicate that experimental treatments to preserve the GCL and rescue vision using this optic nerve injury model would not require additional strategies to preserve the ONL.

Headache After Vaccination: An Update on Recent Clinical Trials and Real-World Reporting.

PURPOSE OF REVIEW: The aim of this review is to characterize headache as a vaccine adverse event (VAE) in clinical trials. RECENT FINDINGS: Of the recent phase III vaccine RCTs (non-COVID-19), 53 studies reported on headache (13 infectious agents). The median rate (interquartile range) of headache was 15.6% (IQR: 9.6-37.6%). Of these, 24.5% of the RCTs reported headache greater in the vaccine group compared to the placebo/control group. In the herpes zoster vaccination trials, headache was more common in all active groups: median rate 33.9% (IQR: 29.7-40.5%) as compared to placebo: median rate 17.7% (IQR: 15.4-23.8%). Influenza and HPV vaccination trials were the 2nd and 3rd most common to have headache as a VAE. Of the 6 widely distributed COVID-19 vaccinations, median rate of post-vaccination headache was 39% (IQR: 28-50%). Headache is a common VAE in vaccine trials. Standardized grading methods, predictors of persistence, and treatment regimens are warranted.

Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases.

Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection, cell stress, neuronal disease, and tumors. Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity. The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27, its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases. Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system. Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain. Interleukin-27 is secreted from and binds to infiltrating microglia, macrophage, astrocytes, and even neurons and it promotes neuronal survival by regulating pro- and anti-inflammatory cytokines, neuroinflammatory pathways, oxidative stress, apoptosis, autophagy, and epigenetic modifications. However, interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations. In this review, we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain, spinal cord, and retina. We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.