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Marialaura Amadio
University of Pavia, Italy
Abstract: 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.
Piotr Rodak
Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, Poland
Abstract: Deficiency of estrogens during the postmenopausal period is an important risk factor for neurodegenerative diseases. Estradiol deficiency can accelerate apoptotic cell death of retinal ganglion cells (RGC), mediated by TNF-receptor family (e.g., FasR/FasL pathway). Since the RGC are part of central nervous system, they are unable to regenerate in case of damage.
In the pilot study, we evaluated the impact of surgical menopause on the function and survival of RGC in the rat model of optic nerve crush (ONC). We used 8-weeks old female long evans rats, divided into 2 main groups depending on the time between ovariectomy procedure (OVE) and euthanasia (2 vs 7 weeks), and subgroups - OVE, OVE+ONC, or ONC. Retinal function was assessed in electroretinography (ERG). RGC loss was evaluated by manual counting using ImageJ software. 7 weeks after OVE, the surgical menopause induced significant retinal interneurons loss, but not RGC loss, however, when the ONC procedure was applied, RGC appeared to be more susceptible to death in estrogens deprivation. In ERG analysis, photopic negative responses were severely diminished in OVE+ONC group. Estrogens deprivation in menopause induced accelerated retinal neurodegeneration that firstly involves retinal interneurons. The lack of estrogens increases susceptibility of RGC to the insult.
Funding: NCN PRELUDIUM 2021/41/N/NZ4/01271
Joanna Machowicz
Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice,
Katowice, Poland
Abstract: Selective serotonin reuptake inhibitors have shown many antiapoptotic and neuroprotective effects by increasing BDNF content in the retina and by reducing conductivity of electrical synapses, thus limiting secondary neurodegeneration of Retinal Ganglion Cells (RGC) and retinal interneurons (RI). 14 Long Evans rats were treated orally with Escitalopram or PBS for 12 weeks. After 8 weeks, transient elevation of intraocular pressure was inducted in the right eye in order to induce retinal ischemia (IC). Electroretinography (ERG) was performed in a few time points. 4 weeks later, rats were sacrificed and retinas and optic nerves were isolated.
A loss of RGC density was noted in the ischemic retina treated with PBS that was not noticed in the group treated with Escitalopram (261±118 vs. 392±92 p<0,05). In the Escitalopram-treated group, scotopic amplitudes of all oscillatory potentials (OP) measured in ERG were significantly higher 14 days after IC induction (p<0,05), while in the control group deep disturbance of RI function was observed, expressed in significant reduction of OP amplitudes (p<0.05).
Oral treatment with Escitalopram prevents desynchronization of RI function during ischemic conditions in a rat model. Observations presented above may become crucial for new therapeutic methods for vascular pathologies of the retina.
Anna Pacwa 1, 2
1 Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, Poland
2GlaucoTech, Katowice, Poland
Abstract: The degeneration of Retinal Ganglion Cells (RGC) is a common process that with slow rate appears over the time and is related to aging. Additional external stimuli, like ischemia, increased intraocular pressure or inflammation, may accelerate this age-related cell death and, by impairing RGC function, lead to blindness. The neuroprotective mechanisms aim to limit the negative chain-reactions induced by the insult, prolonging the survival of RGC. Interestingly, ELAVL1 protein has been recognized as a regulator factor of most stress response-involved proteins, placing it in the position of a pivotal element in the chain of neuroprotective pathways. We showed that AAV-based silencing of hur gene inclines the retina to senescence in healthy rats, and leads to pronounced RGC death in the glaucoma model. Additionally, we report that intravitreally injected Metallothionein II, which exerts benefits in glaucomatous rat retina, fails to protect RGC when applied in hur-silenced animals.
