Evaluation of retinal physiology throughout the development of glaucoma: study of changes in biological rhythm, synthesis of melatonin and opsins

• Grant number: 20/13615-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2021
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Grantee: Helena Guimarães Rosa
• 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 intrinsically photosensitive ganglion cells (ipRGCs), located in the retina, promote a connection between the environment and the whole-body physiology. Since ipRGCs express the photopigment melanopsin (OPN4), they have the ability to convert the photic information into an action potential and signalling it to different brain areas, including the suprachiasmatic nucleus (SCN), which is known as the central biological clock. The retinal neurons, as the SCN ones, transmit the photic information to other ocular areas by humoral signaling, mainly through the production of melatonin, in this way, melatonin can act as a synchronize cue regulating the ocular physiology once that other structures than retina seem not to be capable of directly detect light. Among melatonin functions, it contributes to the aqueous humor production and, consequently, to the intraocular pressure (IOP) modulation. Additionally, melatonin present antioxidant properties once it works as a scavenger of free radical and induce the transcription, and activation of antioxidant enzymes. Glaucoma is a progressive and chronic optic neuropathy, characterized by alteration of the optic nerve and the retinal ganglion cells layer. DBA/2J mice in the early stage of glaucoma exhibits abnormal mitochondria, reduction of its cristae volume and, consequently, reduced NAD+ levels which makes them more vulnerable to neural damages. In this way we intend to stablish the link between IOP and the gene expression of key enzymes of melatonin synthesis in the retina of mice over development of glaucoma in order to understand how this tissue respond to stress caused by ganglion cell's death. With this project. we aim to evaluate the mRNA expression of the melatonin synthesis enzymes, clock genes and opsins in the retina of glaucomatous mice, in order to follow the physiological changes that occur in retina throughout the pathology development.