Light inputs to dopaminergic amacrine cells of the mammalian retina

Background: The retina responds to light over a wide range of operational conditions, surpassing 10 units in a logarithmic scale. Adaptation of the retina to the particular presenting light conditions relies considerably on modulation of retinal pathways by dopamine, which is released in response to light or circadian rhythms exclusively from dopaminergic amacrine cells. Rods, cones and intrinsically photoresponsive retinal ganglion cells (ipRGCs) have all been shown to input into dopaminergic amacrine cells. However, the pathways that these photoreceptors employ to ultimately trigger dopamine release in response to light remain unclear. Methods: Ultra-high performance liquid chromatography separation and tandem mass spectrometry detection was used to quantify dopamine, and its primary metabolite 3,4-dihidroxyphenylacetic acid (DOPAC). Retinal dopamine release was assessed under various conditions, in a variety of mouse models, using two complementary experimental designs: in vivo anaesthetised mice and ex vivo explanted retinae. Conclusions: This thesis provides novel evidence about dopamine dynamics in a variety of light conditions, transgenic mouse models and presence of pharmacological agents. Surprisingly, I found that rod input is both necessary and sufficient to evoke light-induced release dopamine across a wide range of light intensities, without quantifiable contribution from cones or ipRGCs, suggesting that electrophysiological inputs do not match dopamine release. Further, this data suggests that the main pathway that drives this increase in light-induced dopamine release at light intensities where rods should be saturated is the primary rod pathway (with smaller contributions from the secondary and tertiary pathways) and involves bleaching adaptation of rods

Light and myopia: from epidemiological studies to neurobiological mechanisms

Myopia is far beyond its inconvenience and represents a true, highly prevalent, sight-threatening ocular condition, especially in Asia. Without adequate interventions, the current epidemic of myopia is projected to affect 50% of the world population by 2050, becoming the leading cause of irreversible blindness. Although blurred vision, the predominant symptom of myopia, can be improved by contact lenses, glasses, or refractive surgery, corrected myopia, particularly high myopia, still carries the risk of secondary blinding complications such as glaucoma, myopic maculopathy, and retinal detachment, prompting the need for prevention. Epidemiological studies have reported an association between outdoor time and myopia prevention in children. The protective effect of time spent outdoors could be due to the unique characteristics (intensity, spectral distribution, temporal pattern, etc.) of sunlight that is lacking in artificial lighting. Concomitantly, studies in animal models have highlighted the efficacy of light and its components in delaying or even stopping the development of myopia and endeavoured to elucidate possible mechanisms involved in this process. In this narrative review, we (1) summarize the current knowledge concerning light modulation of ocular growth and refractive error development based on studies in human and animal models, (2) summarize potential neurobiological mechanisms involved in the effects of light on ocular growth and emmetropization and (3) highlight a potential pathway for the translational development of noninvasive light-therapy strategies for myopia prevention in children.info:eu-repo/semantics/publishedVersio

Underlying Mechanisms of Epilepsy

This book is a very provocative and interesting addition to the literature on Epilepsy. It offers a lot of appealing and stimulating work to offer food of thought to the readers from different disciplines. Around 5% of the total world population have seizures but only 0.9% is diagnosed with epilepsy, so it is very important to understand the differences between seizures and epilepsy, and also to identify the factors responsible for its etiology so as to have more effective therapeutic regime. In this book we have twenty chapters ranging from causes and underlying mechanisms to the treatment and side effects of epilepsy. This book contains a variety of chapters which will stimulate the readers to think about the complex interplay of epigenetics and epilepsy

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40