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Adenosine A2A Receptor: A New Neuroprotective Target in Light-Induced Retinal Degeneration
Manuel Soliño1, Ignacio M Larrayoz2, Ester María López1
1Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
Frontiers in Pharmacology
|April 7, 2022
Summary
Blocking adenosine A2A receptors protected against light-induced retinal degeneration in rats. This suggests A2A receptor antagonists may be a potential treatment for outer retinal degenerative diseases.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Continuous light exposure causes photoreceptor degeneration, modeling human outer retinal diseases like age-related macular degeneration.
- Adenosine A2A receptors play a role in retinal physiology and pathology.
Purpose of the Study:
- To investigate the neuroprotective potential of modulating adenosine A2A receptor activity in a rat model of light-induced retinal degeneration.
Main Methods:
- Rats received intravitreal injections of an adenosine A2A receptor agonist (CGS 21680) or antagonist (SCH 58261).
- Eyes were subjected to continuous high-intensity light exposure.
- Retinal damage was assessed using immunohistochemistry (GFAP), TUNEL assay, Western blotting, qRT-PCR, and electroretinography.
Main Results:
- CGS 21680 treatment increased apoptosis and glial activation but did not affect function.
- SCH 58261 treatment reduced apoptosis, glial activation (GFAP), and activated caspase-3 levels.
- SCH 58261 preserved retinal function, evidenced by improved electroretinography amplitudes, and decreased pro-inflammatory cytokine expression (TNF-α).
Conclusions:
- Adenosine A2A receptor blockade before light exposure demonstrates significant neuroprotection against retinal damage.
- A2A receptor antagonists show promise for treating light-induced and potentially other retinal degenerative diseases.
