"Participation of purinergic signals in the activation and death of multipotent progenitor cells in the regeneration process of the zebrafish retina"

FAILLACE MARÍA PAULA

Curitiba

Congreso; XII MEETING OF THE BRAZILIAN PURINE CLUB; 2023

Clube de Purinas y Universidade Federal do Parana, BRAZIL

Participation of purinergic signals in the activation and death of multipotent progenitor cells in the regeneration process of the zebrafish retina.Author: Maria Paula FaillaceDepartamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires. Instituto de Fisiología y Biofísica (IFIBIO)-Houssay, UBA-CONICET. Ciudad de Buenos Aires, ARGENTINA. Email. mfaillace@fmed.uba.arThe zebrafish retina is known as an excellent experimental model to study the regeneration of tissue in the central nervous system of adult vertebrates. The zebrafish retina can regenerate all neurons from multipotent progenitors represented by Müller glia. Müller glia undergo reprogramming and re-entry into the cell cycle, which are activated by injury. Mitotic division of Müller glia generates many daughter progenitor cells that migrate to the retinal layers and differentiate into mature neurons, restoring retina function and vision. We have characterized chemical lesions with cytotoxic and hypoxic components to damage the zebrafish retina. These chemical injury models were used to better understand the role of extracellular nucleotides and adenosine and P2y1, P2X7, and P1 receptors in the regeneration process of the zebrafish retina. Moreover, excessive stimulation of P2X7R by BzATP caused injury-like effects that could be used as a model of retinal damage. We observed that nucleotide depletion or blocking of P2y1R, P2X7R, and P1R (including A2AR) during the regeneration process induced by chemical injury significantly increases the effect of damage on neurons, microglia and blood vessels and prevent proliferation of progenitors and later, cell differentiation. Our findings indicate an important role of purine signaling in controlling the severity of damage and the regenerative process, regulating cell death, proliferation and differentiation of progenitor and mature cells of the zebrafish retina.