Evaluation of the pharmacological mechanisms of the TnP peptide in the therapy of retinopathy in Zebrafish

• Grant number: 24/08193-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): August 01, 2024
• Effective date (End): December 20, 2024
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Monica Valdyrce dos Anjos Lopes Ferreira
• Grantee: João Gabriel dos Santos da Rosa
• Supervisor: Breandan Kennedy
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Research place: University College Dublin, Ireland
• Associated to the scholarship: 21/08891-8 - Assessment of the pharmacological mechanisms of the peptide TnP isolated from Thalassophryne nattereri venom in the therapy of Hypoxic Retinopathy in Zebrafish, BP.PD

Abstract

The project focuses on exploring the therapeutic potential of the TnP family, derived from the venom of the Brazilian fish Thalassophryne nattereri, particularly in the context of retinopathy. This family comprises synthetic peptides with immunomodulatory properties, as demonstrated in studies using murine models of Multiple Sclerosis (EAE). Research has shown that TnP, administered subcutaneously, has promising anti-inflammatory effects. Expanding beyond murine models, the therapeutic efficacy of TnP has also been validated in zebrafish models. The zebrafish, due to the conservation of retinal function and anatomy with humans, serves as a valuable model for the study of retinal degenerations. Whether induced by environmental factors, aging, or genetics, retinal degenerations share common mechanisms with human pathologies such as retinopathy of prematurity and glaucoma. In this project, we aim to evaluate the potential of TnP to inhibit the development of retinopathy or treat retinopathy using zebrafish larvae at 72 hours post-fertilization (hpf). Two models of retinopathy induction will be employed: hypoxic retinopathy induced by exposure to cobalt chloride (CoCL2) or light-induced retinal damage (LIRD) by intense exposure to light. Larvae, with induced retinopathy or normal, will be treated with TnP dissolved in 0.5× E2 medium at a concentration of 100 ¼M during the induction period. To evaluate the therapeutic efficacy of PnT, locomotor changes in larvae with retinopathy will be evaluated by means of visual motor response (CABG), measuring the total distance traveled. Additionally, the extent of retinal damage will be assessed through histological analysis of whole larval tissues, sectioned at 18 ¼m in the coronal position and stained with hematoxylin and eosin (H&E). In addition, to increase the depth of our observations, different transgenic zebrafish strains expressing specific markers for various retinal cell types will be utilized. This approach will allow us to discern the effects of TnP on different cellular components within the retina, providing valuable insights into its mechanisms of action. Through this comprehensive approach, we aim to elucidate the prophylactic and therapeutic potential of TnP in relation to retinopathy by leveraging the versatility of zebrafish models for translational research.