Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Method: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

PurposeTo evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo.MethodsTwenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography.ResultsThe overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 μg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 μg/mL, 44.45 ± 10.19 μg/mL and 330.41 ± 75.8 μg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 μg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 μg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 μg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 μg/mL, 6.24 ± 3.6 μg/mL and 172.80 ± 99.76 μg/mL, respectively.ConclusionCiticoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.

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Background. A plethora of inflammatory, angiogenic, and tissue remodeling factors has been reported in idiopathic epiretinal membranes (ERMs). Herein we focused on the expression of a few mediators (oxidative, inflammatory, and angiogenic/vascular factors) by means of short-term vitreal cell cultures and biomolecular analysis. Methods. Thirty-nine (39) ERMs and vitreal samples were collected at the time of vitreoretinal surgery and biomolecular analyses were performed in clear vitreous, vitreal cell pellets, and ERMs. ROS products and iNOS were investigated in adherent vitreal cells and/or ERMs, and iNOS, VEGF, Ang-2, IFNγ, IL18, and IL22 were quantified in vitreous (ELISA/Ella, IF/WB); transcripts specific for iNOS, p65NFkB, KEAP1, NRF2, and NOX1/NOX4 were detected in ERMs (PCR). Biomolecular changes were analyzed and correlated with disease severity. Results. The higher ROS production was observed in vitreal cells at stage 4, and iNOS was found in ERMs and increased in the vitreous as early as at stage 3. Both iNOS and NOX4 were upregulated at all stages, while p65NFkB was increased at stage 3. iNOS and NOX1 were positively and inversely related with p65NFkB. While NOX4 transcripts were always upregulated, NRF2 was upregulated at stage 3 and inverted at stage 4. No significant changes occurred in the release of angiogenic (VEGF, Ang-2) and proinflammatory (IL18, IL22 and IFNγ) mediators between all stages investigated. Conclusions. ROS production was strictly associated with iNOS and NOX4 overexpression and increased depending on ERM stadiation. The higher iNOS expression occurred as early as stage 3, with respect to p65NFkB and NRF2. These last mediators might have potential prognostic values in ERMs as representative of an underneath retinal damage.