GIRARDI Elena Silvia
Adenosine A1 receptor: A neuroprotective target in light induced retinal degeneration
MANUEL SOLIÑO, ESTER MARIA LOPEZ,MANUEL REY-FUNES, CESAR FABIAN LOIDL; IGNACIO M. LARRAYOZ, ALFREDO MARTINEZ; ELENA GIRARDI; JUAN JOSE LOPEZ COSTA
PUBLIC LIBRARY SCIENCE
Lugar: San Francisco; Año: 2018
PLoS One. 2018 Jun 18;13(6):e0198838. doi:10.1371/journal.pone.0198838. eCollection 2018.AdenosineA1 receptor: A neuroprotective target in light induced retinal degeneration.Soliño M1,2, López EM1,2, Rey-Funes M1,2, Loidl CF1,2, Larrayoz IM3, Martínez A4, Girardi E1,2, López-Costa JJ1,2.Author informationAbstractLightinduced retinal degeneration (LIRD) is a useful model that resembles humanretinal degenerative diseases. The modulation of adenosine A1 receptor isneuroprotective in different models of retinal injury. The aim of this work wasto evaluate the potential neuroprotective effect of the modulation of A1receptor in LIRD. The eyes of rats intravitreally injected withN6-cyclopentyladenosine (CPA), an A1 agonist, which were later subjected tocontinuous illumination (CI) for 24 h, showed retinas with a lower number of apoptoticnuclei and a decrease of Glial Fibrillary Acidic Protein (GFAP) immunoreactivearea than controls. Lower levels of activated Caspase 3 and GFAP weredemonstrated 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 byimmunohistochemistry. Electroretinograms (ERG) showed higher amplitudes ofa-wave, b-wave and oscillatory potentials after CI compared to controls.Conversely, the eyes of rats intravitreally injected withdipropylcyclopentylxanthine (DPCPX), an A1 antagonist, and subjected to CI for24 h, showed retinas with a higher number of apoptotic nuclei and an increaseof GFAP immunoreactive area compared to controls. Also, higher levels ofactivated Caspase 3 and GFAP were demonstrated by Western Blot. The mRNA levelsof iNOS, nNOS and inflammatory cytokines (IL-1β and TNFα) were not modified by DPCPX treatment. An increase ofIba 1+/MHC-II+ reactive microglial cells was shown by immunohistochemistry. ERGshowed that the amplitudes of a-wave, b-wave, and oscillatory potentials afterCI were similar to control values. A single pharmacological intervention priorillumination stress was able to swing retinal fate in opposite directions: CPAwas neuroprotective, while DPCPX worsened retinal damage. In summary, A1receptor agonism is a plausible neuroprotective strategy in LIRD.