Neuroprotection in a glaucoma model by Saffron extract oral supplementation

Abstract

AbstractPurposeTo study whether saffron extract supplementation can decrease microglial activation signs and reduce retinal ganglion cells (RGCs) loss in a glaucoma model.MethodsAlbino Swiss mice groups; naïve (NG n = 6), saffron naïve (SNG n = 8), laser 3 days (LG3d n = 8), laser 7 days (LG7d n = 6), saffron laser 3 days (SLG3d n = 8) and saffron laser 7 days (SLG7d n = 6). In laser groups, unilateral ocular hypertension (OHT) was induced by OI laser photocoagulation. OHT and contralateral eyes were analysed. Retinal whole‐mounts were processed: (1) Anti Iba‐1 to quantify: Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); Area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ganglion cell layer (NFL‐GCL); Cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; and Arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL. (2) Anti‐P2RY12 for resident microglia. 3) Anti‐Brn3a to quantify Brn3a+ RGCs number.ResultsNo differences were found between naïve groups. LG3d OHT eyes showed significant: increase of Ibacn, Iba‐1 RA and CbIbac and decrease of AAIbac compared to NG. In SLG3d, OHT and contralateral eyes showed a significant reduction of microglial activation signs compared to LG3d. In NG all Iba‐1 + cells were P2RY12+. Compared to NG, in LG3d OHT eyes, the P2RY12 expression was down‐regulated. In SLG3d OHT eyes, saffron extract led to a smaller decrease. In contralateral eyes of LG3d and SLG3d, P2RY12 expression was similar to NG. In LG7d OHT eyes, a significant reduction in the number of Brn3a+ RGCs compared to NG was observed. Saffron extract counteracted this reduction and a significant different were found in SLG7d OHT eyes respect to LG7d OHT eyes. No differences were found between LG7d and SLG7d contralateral eyes.ConclusionsSaffron extract decreases the morphological signs of microglial activation, down‐regulation of P2RY12 and counteract the RCGs loss. Thus, they reduce neuroinflammation associated with IOP increase and protect RGCs.