Bone Marrow-Derived Mononuclear Cell Transplants Decrease Retinal Gliosis in Two Animal Models of Inherited Photoreceptor Degeneration.

Inherited photoreceptor degenerations are not treatable diseases and a frequent cause of blindness in working ages. In this study we investigate the safety, integration and possible rescue effects of intravitreal and subretinal transplantation of adult human bone-marrow-derived mononuclear stem cells (hBM-MSCs) in two animal models of inherited photoreceptor degeneration, the P23H-1 and the Royal College of Surgeons (RCS) rat. Immunosuppression was started one day before the injection and continued through the study. The hBM-MSCs were injected in the left eyes and the animals were processed 7, 15, 30 or 60 days later. The retinas were cross-sectioned, and L- and S- cones, microglia, astrocytes and Müller cells were immunodetected. Transplantations had no local adverse effects and the CD45+ cells remained for up to 15 days forming clusters in the vitreous and/or a 2-3-cells-thick layer in the subretinal space after intravitreal or subretinal injections, respectively. We did not observe increased photoreceptor survival nor decreased microglial cell numbers in the injected left eyes. However, the injected eyes showed decreased GFAP immunoreactivity. We conclude that intravitreal or subretinal injection of hBM-MSCs in dystrophic P23H-1 and RCS rats causes a decrease in retinal gliosis but does not have photoreceptor neuroprotective effects, at least in the short term. However, this treatment may have a potential therapeutic effect that merits further investigation.

Antioxidant Activity and Neuroprotective Role of Docosahexaenoic Acid (DHA) Supplementation in Eye Diseases That Can Lead to Blindness: A Narrative Review.

The objective of this narrative review is to provide updated evidence, based on data from experimental and clinical studies, of the prominent role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) for a number of crucial mechanisms involved in counteracting cell damage induced by oxidative stress in eye diseases. This article is focused on the antioxidant and neuroprotective effects of docosahexaenoic acid (DHA), which have been assessed in different experimental models and clinical studies, particularly in proliferative diabetic retinopathy, age-related macular degeneration and glaucoma that are the most common eye diseases leading to severe vision loss. The mechanisms involved in the role of DHA in protecting human retinal pigment epithelial cells from oxidative stress as well as the interaction with glutathione (GSH) are also described. The review is intended to provide novel and salient findings supporting the rationale of the use of dietary supplementation with high-dose DHA (1050 mg/day) in the form of triglyceride as a potent antioxidant compound for improving the eye health. However, the overall clinical evidence for the use of dietary strategies based on supplementation with n-3 PUFAs in eye diseases linked to oxidative stress other than high-dose DHA triglyceride is both limited and inconsistent.

Supplementation with a highly concentrated docosahexaenoic acid plus xanthophyll carotenoid multivitamin in nonproliferative diabetic retinopathy: prospective controlled study of macular function by fundus microperimetry.

OBJECTIVE: There is little evidence of real-life outcomes of dietary supplementation with high-dose docosahexaenoic acid (DHA) and carotenoids in patients with diabetic retinopathy (DR). We assessed the effect of supplementation with DHA triglyceride (1,050 mg/d) + xanthophyll carotenoid multivitamin on macular function in nonproliferative DR. METHODS: Asymptomatic patients with nonproliferative DR were included in a prospective controlled study and assigned (1:1) to the DHA supplementation group or the control group. Macular sensitivity and macular integrity area were the main outcome measures. Functional vision measures (macular function [MAIA™ CenterVue], best-corrected visual acuity), structural retinal measures (central subfield macular thickness), and biochemical parameters (plasma total antioxidant capacity, DHA content of the erythrocyte membrane, and plasma IL-6) were evaluated at baseline and after 45 and 90 days of DHA supplementation. RESULTS: The study included 24 patients (48 eyes) (12 patients, 24 eyes in each group). Baseline clinical characteristics of patients in both groups were similar. Macular sensitivity increased from a mean (SD) of 25.9 (2.4) dB at baseline to 27.3 (2.3) dB at 90 days (P=0.030) in the DHA group only (between-group differences P<0.19). The macular integrity index decreased from 71.2 (33.2) at baseline to 63.5 (36.4) at 45 days and to 51.6 (35.9) at 90 days (P=0.002) in the DHA group only (between-group differences P<0.05). Best-corrected visual acuity and central subfield macular thickness did not vary significantly in any of the comparisons and in none of the groups. DHA content of erythrocyte membrane and total antioxidant capacity levels increased significantly only in the DHA group. Plasma IL-6 levels decreased significantly only in the DHA group. CONCLUSION: In an early stage of DR, supplementation with high-dose DHA plus xanthophyll carotenoid multivitamin during 90 days was associated with a progressive and significant improvement of macular function measured by microperimetry. Biochemical changes supported the effect of DHA.