Retinal protection of a new nutraceutical formulation.

Abstract

Purpose : Retinal ganglion cells (RGCs) protection is challenging and represent an unmet medical need in glaucoma management. We assessed the neuroprotective and anti-inflammatory effect of a new nutraceutical formulation in vitro and in vivo.

Methods : Neuroblastoma cells (SH-SY5Y) challenged with staurosporine, were treated with the new formulation (Epicolin™) or with its single components [citicoline (C), homotaurine (O), epigallocatechin gallate (EGCG), coleus forskohlii (F), B1, B2, B3, B6, B9 and E vitamins], and cell viability was evaluated after 24h. Three additional formulations were also tested in vitro: FC (C, inulin, zinc, B5 and B8); FG (O, mint extract, F, B1, B2, B3, B6 and B12) and FN (C, O and vit E). The in vivo study was carried out in DBA/2J mice (7 months) conformed with ARVO resolution on the use of animals in research. Epicolin-treated group (208.6 mg/kg once a day by oral route, for 5 weeks) vs. vehicle (CTRL) was compared in terms of retinal function. RGCs function was evaluated by pattern electroretinogram (PERG) at basal, 3 and 5 weeks. At the end of treatment, animals were killed and retinas collected. Immunostaining for RBPMS on retinal flat mounts was carried out to assess RGCs density. Biomarkers, such as BDNF, IL1b and TNFa were analyzed by RT-PCR. Post-hoc tests were performed after ANOVA.

Results : The in vitro study demonstrated that EGCG exerted a significant (p≤0.001) protective effect on SH-SY5Y compared to CTRL cells (Fig. 1). In particular, Epicolin showed a higher protective effect (p≤0.01) even compared to EGCG treated cells (Fig. 1). Conversely, all other formulations (FC, FG and FN) did not show a protective effect compared to Epicolin (p≤0.0001). Results from PERG demonstrated a significant (p<0.001) protection of retinal function in the Epicolin treated group vs. CTRL (p≤0.001; Fig.2). Moreover, Epicolin treatment attenuated RGCs death (RBPMS staining), enhancing BDNF (p≤0.05) expression and reducing TNF-α and IL-1β levels (p≤0.05) in the retina.

Conclusions : These data suggest that Epicolin could be useful to attenuate the progression of glaucoma. Indeed, Epicolin improved neuronal cell viability, preserved RGCs function, reduced retinal inflammation and induced the expression of the neurothropic factor BDNF. In conclusion, Epicolin may be useful as a adjuvant therapy for glaucomatous patients, even though clinical studies are needed to support that.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.