Lycium barbarum extracts preserve retinal function by rescuing synaptic loss in 3XTG mouse model of Alzheimer’s disease

Abstract

AbstractBackgroundOcular abnormalities were reported in patients with Alzheimer’s disease (AD). The Lycium barbarum extracts (LBE) have been demonstrated to be neuroprotective. The current study aim to investigate the effect of oral feeding LBE on structural and functional changes of retina in the 3xTg AD mouse model.Method6 months old 3xTg‐AD and C57/6J mice were treated by gavage with low (200mg/kg) or high (2g/kg) doses of LBE daily for 3 months, while water treatment was used as a placebo control. Retinal function was evaluated by electroretinogram (ERG). Mice were sacrificed after 3 months of treatment, and the eyes were harvested. Morphological changes of the retina were analyzed in cross‐sections. Expressions of synaptophysin, PSD95, 8‐OHG, Calpain2, and Calpain5 were detected by Immunohistochemical staining.ResultERG results showed that the scotopic retinal response of 3xTg‐AD mice started to decline at 4–6 months of age, followed by a rapid decrease at 6–8 months of age. In this study, one month high doses LBE gavage group showed a significant increase of b‐wave in scotopic ERG. The same tendency of b‐wave preservation was observed at two months post high doses LBE feeding without statistical significance and vanished at three months (9 months of age). In 9 months old AD mice, no significant changes were observed in inner nuclear layer (INL) thickness and outer nuclear layer (ONL) thickness compared to age‐matched C57 mice. Accordingly, there were no significant differences in retinal ganglion cell and bipolar cell numbers between AD mice and C57 mice. However, presynaptic density in INL but not ONL was decreased in AD mice. This synapse loss could be rescued by LBE feeding with significance in high dose. IHC staining revealed highly expressed 8‐OHG, Calpain2 and Calpain5 in AD mice, which were downregulated by LBE feeding in a dose dependent manner.ConclusionOur results indicated that at early‐ and mid‐stage of AD, presynaptic changes in IPL contributed to b‐wave decline and LBE gavage could rescue the retinal functional deterioration in 3xTg AD mice by preventing the synapse loss in IPL through inhibiting oxidative stress and lowering Ca2+ in retinas.