PRE2023-Role of innate immunity and microglial senescence on the structural and functional alterations associated to neurodegeneration in retinitis pigmentosa (PID2022-138917OB-100

We study Retinitis Pigmentosa (RP), a rare disease that includes a group of hereditary retinal dystrophies. RP leads to blindness due to the dysfunction and death of photoreceptors. Its genetic complexity, with more than 80 genes and 3000 mutations involved, and the absence of effective, preventive or curative treatment constitute an important scientific-medical challenge. Innate immunity, considered the most primitive line of defense against infections, is involved in neurodegenerative processes. Cells that mediate the innate immune response, particularly microglia, contribute to generating a state of sterile inflammation whose role in neurodegeneration is controversial. The PhD student will characterize the role of the innate immune response in the course of retinal neurodegeneration in RP. In this context, we will study the contribution of Toll-like receptors (TLR), innate immunity receptors that are part of the microglia sensome, as well as of damage signaling molecules or alarmins to the reactive state of microglia and infiltration of peripheral myeloid cells. We aim to determine the role of microglia activation in the death of photoreceptors and the loss of visual function. We pursue to define the potential role of actors of innate immunity in the degenerative process and whether their modulation could confer neuroprotection, generating new therapeutic targets.