CHRONIC THYROID HORMONE EXCESS INDUCES ANGIOGENESIS AND NEURONAL DEATH IN THE ADULT ZEBRAFISH RETINA

PABLO IOMINI; LEANDRO ROCCO; ALEJANDRO BEJARANO ; RAMON BERNABEU ; MARIA PAULA FAILLACE

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2022 (SAIC; SAI-FAIC; SAFIS); 2022

Sociedad Argentina de Investigación Clìnica (SAIC), Sociedad Argentina de Fisiología (SAFIS) y Sociedad Argentina de Inmunologia (SAI) y FAIC (Congreso Franco-Argentino de Inmunología)

CHRONIC THYROID HORMONE EXCESS INDUCESANGIOGENESIS AND NEURONAL DEATH IN THE ADULT ZEBRAFISH RETINAAdult zebrafish are capable of regenerating organs and tissuesover their life span including brain, the spinal cord and retina. So, zebrafishare suitable experimental vertebrate models to identifysignalling systems thatcontrol cell genesis and differentiation in the nervous system. Central nervoussystem development and growth depend on thyroid hormones (TH)regulating cellproliferation, differentiation and patterning. TH signaling controlsmetabolismandcell growth throughout lifetime.So, we aimed to examine whether TH disequilibrium affected adultretina growth and regeneration. To this end, ouabain (20 µM) was intraocularly injected provokinga medium severity retina injury. Then, control orinjured zebrafish were treatedwith high doses of thyroxine (T4)(or vehicle) diluted in fish tankwater over 8-, 25- and 60-day periods. After a week, zebrafish lost melanin intheir skin melanocytes which is a sign of hyperthyroidism. ANOVA andBonferronitests were applied to analyze significant changes in cell numbers quantified onretinal layers and relative amounts of different gene mRNA levels were analyzedby RT-quantitative PCR.  Cell death wasqualitatively assessed by TUNEL and activated Caspase-3. Endothelial vascularcells were detected by lectin Lycopersicumesculentum (tomato) in the inner retina and choroid layers. Chronic treatmentwith T4 caused a significant reduction ofphotoreceptors, interneurons, and ganglion cells 25 and 60 days post injury. T4treatment also caused significant reductions in specific retina cell markermRNAlevels: PKC, GFAP, CNG3, CNG1, Thy1, and Conexin26. T4 treatment increased vascularendothelial growth factor receptor mRNA levels, apoptosis,gliosisand angiogenesis.Sustained high levels of T4inducedproangiogenic and proapoptotic mechanismsthat abrogatedretina regeneration. T4excessinducedmorphological changesin the zebrafish retina that emulate neurodegenerative retinopathies.