Putting non-image forming responses to light into practice
Beyond vision, light triggers a variety of non-image forming responses. Amongst these is the pupillary light reflex, commonly used by ophthalmologists to gauge the function of the optic nerve head. In my talk, I will share some of our latest work on optimizing the use of the pupillary light reflex to detect functional loss in ocular diseases in clinics.
Numbing intraneuronal Tau levels to prevent neurodegeneration in tauopathies
Intraneuronal accumulation of the microtubule associated protein Tau is largely recognized as an important toxic factor linked to neuronal cell death in Alzheimer’s disease and tauopathies. While there has been progress uncovering mechanisms leading to the formation of toxic Tau tangles, less is known about how intraneuronal Tau levels are regulated in health and disease. Here, I will discuss our recent work showing that the intracellular trafficking adaptor protein Numb is critical to control intraneuronal Tau levels. Inactivation of Numb in retinal ganglion cells increases monomeric and oligomeric Tau levels and leads to axonal blebbing in optic nerves, followed by significant neuronal cell loss in old mice. Interestingly, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels by promoting exocytosis of monomeric Tau. In TauP301S and triple transgenic AD mouse models, expression of Numb-72 in RGCs reduces the number of axonal blebs and prevents neurodegeneration. Finally, inactivation of Numb in TauP301S mice accelerates neurodegeneration in both the retina and spinal cord and leads to precocious paralysis. Taken together, these results uncover Numb as a essential regulator of Tau homeostasis in neurons and as a potential therapeutic agent for AD and tauopathies.
Potential involvement and target identification of HuR/ELAVL1 in age-related ocular pathologies – Back to the origin
In the last decades, the post-transcriptional control of gene expression has become an area of intense investigation, delineating a complex scenario where several factors (e.g. RNA-binding proteins, coding and non-coding RNAs) orchestrate the fate of a given transcript. An intriguing hypothesis suggests that loss of RNA homeostasis is a central feature of many pathological states, including eye diseases. Since the elav (embryonic lethal, abnormal visual system) gene discovery in the Drosophila melanogaster, the mammalian ELAV-like family has confirmed its leading role in controlling the RNA metabolism (from splicing to translation) of genes with a key function in many physio-pathological contexts. Some relevant findings suggest the involvement of the HuR/ELAV-like1 member and its potential as a therapeutic target in age-related ocular pathologies.
Evidence for electrical coupling between proximal axons of principal neurons
The seminar will present the origin of the hypothesis of electrical coupling between proximal axons, physiological and immunostaining evidence for the presence of the requisite gap junctions and will explain how electrical coupling could account for very fast network oscillations at >80 hz.
Electrical coupling of optic nerve axons - a novel model of gap junctions' involvement in optic nerve function
Axons in the optic nerve are arranged in bundles and conducting action potential with resistance related to their membrane. Optic nerve axons do not form absolutely independent conductive channels. They are directly coupled by gap junctions formed in majority by neuronal Cx45. Coupling of axons, except known transpassing functions, allows to reduce axonal membrane resistance of optic nerve and accelerates transduction of visual signal. This novel finding have substantial implications for understanding of the pathogenesis of various optic neuropathies and identifies a new potential target for a therapeutic approach.
Electrophysiology application for optic nerve and the central nervous system diseases
Electrophysiology of eye and visual pathway is useful tool in ophthalmology and neurology. It covers a few examinations to find out if defect of vision is peripheral or central. Visual evoked potentials (VEP) are most frequently used in neurology and neuroophthalmology. VEP are evoked by flash or pattern stimulations. The combination of these both examinations gives more information about the visual pathway. It is very important to remember that VEP originate in the retina and reflect its function as well. In many cases not only VEP but also electroretinography (ERG) is essential for diagnosis. The seminar presents basic electrophysiological procedures used for diagnosis and follow-up of optic neuropathies and some of central nervous system diseases which affect vision (mostly multiple sclerosis, CNS tumors, stroke, traumas, intracranial hypertension).