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

MANUEL SOLIÑO, ESTER MARÍA LOPEZ, MANUEL REY-FUNES; CÉSAR FABIÁN LOIDL ; IGNACIO M. LARRAYOZ3, ALFREDO MARTÕÂNEZ4, ELENA GIRARDI1,2, JUAN JOSEÂ LOÂ PEZ-COSTA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018

1932-6203

Light induced retinal degeneration (LIRD) is a useful model that resembles human retinaldegenerative diseases. The modulation of adenosine A1 receptor is neuroprotective in differentmodels of retinal injury. The aim of this work was to evaluate the potential neuroprotectiveeffect of the modulation of A1 receptor in LIRD. The eyes of rats intravitreally injectedwith N6-cyclopentyladenosine (CPA), an A1 agonist, which were later subjected to continuousillumination (CI) for 24 h, showed retinas with a lower number of apoptotic nuclei and adecrease of Glial Fibrillary Acidic Protein (GFAP) immunoreactive area than controls. Lowerlevels of activated Caspase 3 and GFAP were demonstrated by Western Blot (WB) intreated animals. Also a decrease of iNOS, TNFα and GFAP mRNA was demonstrated byRT-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 andoscillatory potentials after CI compared to controls. Conversely, the eyes of rats intravitreallyinjected with dipropylcyclopentylxanthine (DPCPX), an A1 antagonist, and subjected to CIfor 24 h, showed retinas with a higher number of apoptotic nuclei and an increase of GFAPimmunoreactive area compared to controls. Also, higher levels of activated Caspase 3 andGFAP were demonstrated by Western Blot. The mRNA levels of iNOS, nNOS and inflammatorycytokines (IL-1β and TNFα) were not modified by DPCPX treatment. An increase ofIba 1+/MHC-II+ reactive microglial cells was shown by immunohistochemistry. ERG showedthat the amplitudes of a-wave, b-wave, and oscillatory potentials after CI were similar to controlvalues. A single pharmacological intervention prior illumination stress was able to swingretinal fate in opposite directions: CPA was neuroprotective, while DPCPX worsened retinaldamage. In summary, A1 receptor agonism is a plausible neuroprotective strategy in LIRD.