Identificación de moléculas endógenas indicadoras y señalizadoras del daño celular en Retinosis Pigmentaria

Ruiz Navarro, Cristina (2019). Identificación de moléculas endógenas indicadoras y señalizadoras del daño celular en Retinosis Pigmentaria. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Identificación de moléculas endógenas indicadoras y señalizadoras del daño celular en Retinosis Pigmentaria
Author/s:
  • Ruiz Navarro, Cristina
Contributor/s:
  • Hernández Sánchez, Catalina
  • Martín Clemente, Juan Pedro
Item Type: Final Project
Degree: Grado en Biotecnología
Date: June 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

The term ‘Neurodegenerative Disease’ includes a group of disorders of the nervous system with genetic, traumatic or age-associated origin. Those diseases course with death of different cell types, leading to irreversible damage. Current investigations are focused on finding possible inhibitory targets for neuronal dysfunction and cell death during the degenerative process. The retina is a specialized part of the Central Nervous System (CNS) responsible for the caption and processing of the light and is highly conserved among vertebrates. The first step of the phototransduction process, is the conversion of the light energy into a membrane potential which alters the release of neurotransmitters. This process is carried out by the photoreceptors: rods and cones. Retinitis Pigmentosa (RP) comprises a group of hereditary retinal degenerations that course with the selective death of photoreceptors. In many cases, the mutations causing the disease affect genes necessary for phototransduction. There have been described more than 3000 mutations in more than 50 genes. However, in up to 50% of cases, the mutations involved are unknown. Loss of photoreceptor inexorably leads to blindness. Currently there is not available treatment for the vast majority of RP patients. It is known that most of the neurodegenerative diseases course with chronic inflammation. In the retina, the resident microglia, as well as the macroglia cells respond to the neurodegenerative process. However, the precise roles of the retinal glial component in the dysfunction and disappearance of photoreceptors are not entirely clear. Tissue stress produces damage molecules (alarmins) that are sensed by PRR (Pattern Recognition Receptor), normally present in glial cells. Activation of PRR triggers the innate immune response that, when exaggerated or prolonged, may lead to excessive phagocytoses and secretion of pro-inflammatory molecules that can perpetuate the damage, and therefore potentially contribute to the progression of the disease. In this TFG we have characterized the HMGB1 protein as a potential endogenous alarmin and showed that blocking HMGB1 prevent photoreceptor loss in a mouse model of RP (rd10 mouse). HMGB1 is a ubiquitous structural nuclear protein that can be actively released by immune cells under stress. Here, we have shown that HMGB1 is differentially located in WT and rd10 microglial cells. While most of the WT microglia cells displayed nuclear immunostaining for HMGB1, in the rd10 the highest percentage corresponded to microglia cells with cytoplasmic staining, suggesting translocation and potential extracellular release. For interference with HMGB1 we have chosen intravitreal vs subconjunctival administration due to its higher effectiveness. Treatment with A Box, a HMGB1 blocking peptide, preserved photoreceptor cell number and integrity.

More information

Item ID: 57124
DC Identifier: http://oa.upm.es/57124/
OAI Identifier: oai:oa.upm.es:57124
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 30 Oct 2019 09:35
Last Modified: 30 Oct 2019 09:35
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