Glaucoma as a model of chronodisruption: impact on the metabolism

• Grant number: 20/04012-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2020
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Grantee: Pietra Souza Barsanele
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism, AP.JP

Abstract

The retina, through melanopsin-positive ganglion cells, constitutes the main input of light information to entrain the mammalian central oscillator, the suprachiasmatic nuclei (SCN). The clock molecular mechanism in SCN is responsible for the generation of rhythmic function, which is transmitted to other organs, allowing the whole organism to align the internal time in harmony with the external one. The loss of internal temporal relationship among different organs / functions can generate a disruption of the phase synchrony between different organ clocks, a phenomenon known as chronodisruption, which is linked to changes in physiology, leading to a pathological condition. In fact, chronic exposure to low light intensity at night has been related to metabolic and hormonal disfunctions. On the other hand, would individuals with a compromised light transduction to the central clock develop changes in physiological parameters? To answer this question, animals that spontaneously develop glaucoma become an ideal model, since they exhibit progressive degeneration of the retinal ganglion layer. What are the short and long-term consequences of the lack of light exposure? Could secondary pathologies result from glaucoma? The present study aims: to evaluate, during the development and progression of glaucoma, the transcripts in organs related to metabolism through next-generation sequence; to verify the existence of a possible trans-synaptic degeneration between retina and SCN; to establish the causeand-effect relationship between dysregulation of the clock molecular machinery and the development of pathologies in peripheral tissues related to metabolism; to verify if the metabolism of glaucomatous animals could be affected by the activation of the skin photo/thermo-reception system.