Abstract
Background and Purpose. Retina plays a pivotal role in sensory
perception, and degenerative diseases lead to visual deficits. The
therapeutic approach includes anti-inflammatory drugs and new
therapeutic protocols, including Anti-VEGF medicines and monoclonal
antibodies. TnP is a drug candidate in preclinical development indicated
for inflammatory diseases, with the ability to interfere with the
dynamic of immune cells. Zebrafish offer several advantages as a
research model, including genetic similarity with humans. Therefore, we
aim to evaluate the therapeutic effect of TnP on zebrafish retinopathy.
Experimental Approach. We used cobalt chloride-induced (CoCl2)
retinopathy and intense light-induced retinal damage (LIRD) and TnP
prophylactic treatment. Visual motor response and histology were
conducted. Key Results. Swimming pattern of CoCl2-exposed larvae
demonstrated inertia compared to negative-control, and exposure to LIRD
induced a shorter distance covered. Histology revealed that
CoCl2-induced damage or LIRD provoked changes in the retina morphology.
Treatment with TnP did not reverse the reduced distance covered by
CoCl2-damaged or LIRD larvae. TnP failed to reverse all retinal layers
thinned by injury by both protocols, except for the IPL, which seemed to
be restored. We found that TnP acts on INL, probably promoting cell
proliferation and increasing synaptic connections among retinal neurons.
This cell modulating activity could represent neuronal plasticity
activity of TnP. Conclusion and Implications. Our findings support
further exploration of TnP as a therapeutic agent for retinal and
neurodegenerative diseases, given its role in neuronal protection and
immune modulation. Alternatively, TnP might require combination with
other therapeutic agents to enhance its efficacy.