Adenosine A1 receptor: A neuroprotective target in light induced retinal degeneration

• Published in: PloS one 2018-06, Vol.13 (6), p.e0198838-e0198838
• Main Authors: Soliño, Manuel, López, Ester María, Rey-Funes, Manuel, Loidl, César Fabián, Larrayoz, Ignacio M, Martínez, Alfredo, Girardi, Elena, López-Costa, Juan José
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - therapeutic use; Adenosine A1 Receptor Agonists - administration & dosage; Adenosine A1 Receptor Agonists - therapeutic use; Amplitudes; Animals; Apoptosis; Biology and Life Sciences; Biomedical research; Blotting, Western; Brain research; Caspase; Caspase 3 - metabolism; Caspase-3; Cytokines; Degenerative diseases; Diabetes; Diabetic retinopathy; Disease; Disease Models, Animal; Electroretinograms; Electroretinography; Eye (anatomy); Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Hypoxia; IL-1β; Illumination; Immunohistochemistry; Inflammation; Influence; Intravitreal Injections; Ischemia; Light; Macular degeneration; Major histocompatibility complex; Male; Medicine and Health Sciences; Microglial cells; Modulation; mRNA; Neuroprotection; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Nuclei; Pharmacology; Photoreceptors; Polymerase chain reaction; Proteins; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptor, Adenosine A1 - drug effects; Receptor, Adenosine A1 - physiology; Retina; Retina - drug effects; Retina - radiation effects; Retinal degeneration; Retinal Degeneration - drug therapy; Risk factors; Rodents; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0198838

Light induced retinal degeneration (LIRD) is a useful model that resembles human retinal degenerative diseases. The modulation of adenosine A1 receptor is neuroprotective in different models of retinal injury. The aim of this work was to evaluate the potential neuroprotective effect of the modulation of A1 receptor in LIRD. The eyes of rats intravitreally injected with N6-cyclopentyladenosine (CPA), an A1 agonist, which were later subjected to continuous illumination (CI) for 24 h, showed retinas with a lower number of apoptotic nuclei and a decrease of Glial Fibrillary Acidic Protein (GFAP) immunoreactive area than controls. Lower levels of activated Caspase 3 and GFAP were demonstrated by Western Blot (WB) in treated animals. Also a decrease of iNOS, TNFα and GFAP mRNA was demonstrated by RT-PCR. A decrease of Iba 1+/MHC-II+ reactive microglial cells was shown by immunohistochemistry. Electroretinograms (ERG) showed higher amplitudes of a-wave, b-wave and oscillatory potentials after CI compared to controls. Conversely, the eyes of rats intravitreally injected with dipropylcyclopentylxanthine (DPCPX), an A1 antagonist, and subjected to CI for 24 h, showed retinas with a higher number of apoptotic nuclei and an increase of GFAP immunoreactive area compared to controls. Also, higher levels of activated Caspase 3 and GFAP were demonstrated by Western Blot. The mRNA levels of iNOS, nNOS and inflammatory cytokines (IL-1β and TNFα) were not modified by DPCPX treatment. An increase of Iba 1+/MHC-II+ reactive microglial cells was shown by immunohistochemistry. ERG showed that the amplitudes of a-wave, b-wave, and oscillatory potentials after CI were similar to control values. A single pharmacological intervention prior illumination stress was able to swing retinal fate in opposite directions: CPA was neuroprotective, while DPCPX worsened retinal damage. In summary, A1 receptor agonism is a plausible neuroprotective strategy in LIRD.