Despite growing evidence for platelets as active players in infection and immunity, it remains unresolved whether platelets contribute to, or are key elements in the development of neuroinflammation. Using the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, we identified platelet accumulation in the circulation by 7-day postinduction (dpi), ahead of clinical onset which occurs at 13–14 dpi. By inducing platelet depletion between 7 and 16 dpi, we demonstrate an association between platelet accumulation in the spinal cord and disease development. Additionally, we provide evidence for platelet infiltration in the white and gray matter parenchyma, but with different outcomes. Thus, while in white matter platelets are clearly associated with lesions, in gray matter large-scale platelet infiltration and expression of the platelet-specific molecule PF4 are detectable prior to T cell entry. In the retina, platelet accumulation also precedes clinical onset and is associated with significant increase in retinal thickness in experimental relative to control animals. Platelet accumulation increases over the disease course in this tissue, but without subsequent T cell infiltration. These findings provide definitive confirmation that platelet accumulation is key to EAE pathophysiology. Furthermore, they suggest an undescribed and, most importantly, therapeutically targetable mechanism of neuronal damage.

Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the suprachiasmatic nucleus (SCN), which receives information from the short-wavelength-sensitive intrinsically photosensitive retinal ganglion cells. The SCN synchronizes local clocks throughout the body affecting sleep/wake routines and the secretion of neuroendocrine-linked hormones such as melatonin from the pineal gland and cortisol via the hypothalamic pituitary adrenal (HPA) axis. Although the effects of light parameters on melatonin have been recently reviewed, whether the experimental variation of the spectral power distribution and intensity of light can induce changes in cortisol rhythms remains unclear. Thus, this systematic review evaluated the effects of daytime exposure to lights of different spectral wavelength characteristics and luminance intensity on the cortisol levels in healthy individuals. A search of the PubMed, Web of Science, EMBASE, CINAHL, Medline, PsycINFO and Cochrane Library databases on 19 June 2023 identified 3418 articles, of which 12 studies (profiling 337 participants) met the inclusion and risk of bias criteria. An analysis of the literature indicated that exposure to bright lights of any colour during the late night or early morning can induce significant increases in cortisol secretion relative to time-matched dim light comparison conditions. Furthermore, exposure to bright lights with stronger short-wavelength (blue/green) components in the early morning typically induced greater increases in cortisol relative to lights with stronger long-wavelength (red) components. Thus, the circadian regulation of cortisol is sensitive to the wavelength composition of environmental lighting, in line with the more commonly studied melatonin. As such, wavelength characteristics should be optimized and reported in light intervention studies (particularly for the investigation of cortisol-associated disorders and HPA axis function), and exposure to short-wavelength light during sensitive periods should be carefully considered in constructed environments (e.g., bedroom and classroom lighting and device screens).

Purpose: RNA sequencing analysis has demonstrated bidirectional changes in metabolism, structural and immune pathways during early induction of defocus induced myopia. Thus, the aim of this study was to investigate whether similar gene pathways are also related to the more excessive axial growth, ultrastructural and elemental microanalytic changes seen during the induction and recovery from form-deprivation myopia (FDM) in chicks and predicted by the RIDE model of myopia. Methods: Archived genomic transcriptome data from the first three days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 h of normal visual recovery (FDMR) were collected. Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD. Curated gene-sets were obtained from open access sources. Results: Clusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and were found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 h of recovery from 10 days of FDM. Conclusions: The gene pathways altered during induction of FDM are similar to those reported in defocus induced myopia and are established indicators of oxidative stress, osmoregulatory and associated structural changes. These findings are also consistent with the choroidal thinning, axial elongation and hyperosmotic ion distribution patterns across the retina and choroid previously reported in FDM and predicted by RIDE.

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba²⁺ and 10⁻⁵ M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba²⁺ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba²⁺ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia.

Although the McGurk Effect is a well researched illusory phenomenon arising from discrepant auditory and visual speech information little is known about the influence of lexical processes on this phenomenon. Thus, we investigated the McGurk Effect using three letter consonant-vowel-consonant real word and pseudoword pairs with an audiovisual discrepancy positioned at either stimulus onset or offset. The results demonstrated that the frequency of illusions was similar for real words and pseudowords when the discrepancy was at stimulus onset but was significantly lower for real words when the audiovisual discrepancy was positioned at stimulus offset. Positioning of audiovisual discrepancy was not important for accurate auditory perception of pseudowords. These results suggest that the McGurk illusion is the result of audiovisual integration that occurs early in perception prior to word identification and that these early audiovisual integrative processes are modulated by lexical knowledge.