Marialaura Amadio

Symposium Description

Retinal neurons are considered to be part of the central nervous system, resulting in lack of their spontaneous regeneration in response to damage. Glaucoma, a progressive optic neuropathy, is thought to be the main cause of severe visual impairment or permanent vision loss. This type of optic neuropathy is characterized by damage to Retinal Ganglion Cells (RGC) and their axons, which form the optic nerve. RGC death is most commonly a consequence of elevated intraocular pressure (IOP), which has made lowering the IOP, up to now, considered to be the most effective treatment method. However, high IOP is not the only pathological factor, suggesting that glaucoma might be a primary optic nerve disease that makes RGC more prone to respond to risk factors such as increased IOP. The exact mechanism of RGC death in glaucoma is still unknown, although apoptosis has been suggested to be the final common pathway for cell death. There are several stages of RGC damage occurring during the development of glaucoma and RGC death is considered to be a biphasic process. First, one or more trigger factors (i.e. increased IOP, ischemia or simply aging of the organism) evokes the primary, but limited damage to RGC. Subsequently, oxidative stress and excitotoxicity induce secondary damage to surrounding neurons. The chronic neurodegeneration occurs, and intracellular glutamate is released from the dying cells and dispersed among other neighboring cell populations (secondary degeneration), triggering a cascade of excitotoxicity events leading to subsequent cell death. Since current therapeutic strategies are not sufficient to prevent glaucoma-related blindness and to restore the function of already injured RGC, novel therapeutic approaches are expected to be developed to provide sufficient neuroprotection and regeneration of RGC. Here we would like to present novel ideas for RGC neuroprotection related to RNA-binding proteins, estrogen signalling and serotonin pathway modulation. 

Talk: "The role of RNA-binding proteins in the Retinal Ganglion Cells survival"

Increasing evidence suggests that loss of RNA homeostasis is a central feature in many pathological states, including eye diseases. Gene expression is controlled at posttranscriptional level by several factors (e.g. RNA-binding proteins, coding and non-coding RNAs) playing in concert to determine the fate of a given transcript. Among mammalian RNAbinding proteins, the ELAVL (embryonic lethal, abnormal visual system-like) family is a masterpiece of gene expression regulation by affecting RNA metabolism from splicing to translation. The ubiquitous member of this family, HuR/ELAVL1, controls the expression of genes with a key function in physio and pathological contexts. Alterations in HuR/ELAVL1 levels and/or function have been found in some cellular and animal models of age-related ocular diseases. Although the picture is far to be completed, intriguing findings suggest HuR/ELAVL1 involvement in the aetiopathology and its potentiality as a therapeutic target in retinal ganglion cell degeneration.