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Intravitreal Interleukin-2 modifies retinal excitatory circuits and retinocollicular innervation
S A Espírito-Santo1, N Nunes-Tavares2, H R Mendonça3
1Instituto de Biologia, Programa de Pós-Graduação Em Neurociências, Universidade Federal Fluminense, Niterói, Brazil; Instituto de Biofísica, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil; Universidade Do Estado de Minas Gerais, Departamento de Ciências Biológicas, Minas Gerais, Brazil.
Experimental Eye Research
|January 18, 2021
Summary
Interleukin-2 (IL-2) alters retinal neurotransmitter pathways, impacting visual system development. This immune cytokine influences both cholinergic and glutamatergic signaling, suggesting a role in neural plasticity.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Interleukin-2 (IL-2), a known immune cytokine, has largely unexplored neural functions.
- Elevated IL-2 levels are observed in neuropathologies like Alzheimer's disease and multiple sclerosis.
- IL-2 regulates glutamate and acetylcholine transmission, crucial for central nervous system (CNS) physiology.
Purpose of the Study:
- To investigate the impact of increased intravitreal IL-2 on retinal glutamatergic and cholinergic signaling during retinotectal development.
- To explore the mechanisms underlying IL-2-induced axonal plasticity in the developing visual system.
Main Methods:
- HRP neuronal tracing to assess axonal sprouting.
- Protein analysis and immunolocalization to measure pathway activation and neurotransmitter levels.
- Assessing expression of phospho-STAT-3, Egr1, PSD-95, nicotinic acetylcholine receptor β2 subunit, AChE activity, GluN2B, and GluA2.
Main Results:
- Intravitreal IL-2 induced both contralateral and ipsilateral axonal sprouting in the retinotectal system.
- IL-2 activated its pathway via increased phospho-STAT-3 expression.
- Transient reduction in Egr1, PSD-95, and nicotinic acetylcholine receptor β2 subunit levels indicated decreased neural activity and synaptic sites.
- Reduced acetylcholinesterase (AChE) activity and GluN2B/GluA2 content were observed post-IL-2 treatment.
Conclusions:
- Increased intravitreal IL-2 levels alter retinal glutamatergic and cholinergic signaling pathways.
- These neurochemical changes are implicated in IL-2-driven retinotectal plasticity during development.
- IL-2's role extends beyond immunity to influencing CNS development and neural signaling.
