Evaluating TnP as a Potential Therapeutic Agent for Retinopathy in Zebrafish Models

Author(s)

Rosa, Joao Gabriel Santos ; Bernardo, Jefferson Thiago Goncalves ; Alvarez, Yolanda ; Kennedy, Breandan ; Lima, Carla ; Lopes-Ferreira, Monica

• Document type: Journal article
• Source: PHARMACEUTICALS; v. 18, n. 6, p. 16-pg., 2025-06-04.

Abstract

Background: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish-which share significant genetic homology with humans-we investigated TnP's effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl2)-induced hypoxia or light-induced retinal damage (LIRD). Methods: We employed two retinal injury models (CoCl2-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual-motor response testing and histological examination. Results: CoCl2 exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)'s thickness. Conclusions: Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments. (AU)

• FAPESP's process: 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
• Grantee: João Gabriel dos Santos da Rosa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC