Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. HIGHLIGHTS: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Comparison of macular pigment and serum lutein concentration changes between free lutein and lutein esters supplements in Japanese subjects.

PURPOSE: To compare changes in macular pigment optical density (MPOD) and serum lutein concentration between free lutein and lutein esters supplements in healthy Japanese individuals. METHODS: Twenty healthy subjects (age range, 22-47 years) were recruited into this prospective, randomized, doubled-blind comparative study. Individuals were evenly divided into two groups: free lutein group, supplementation with 10 mg of free lutein; or lutein esters group, supplementation with 20 mg of lutein esters equivalent to 10 mg of free lutein. Each participant took either type of oral lutein daily for 3 months. The serum lutein concentrations and MPOD levels were measured at baseline and 3 and 6 months after the start of supplementation. RESULTS: There were no significant differences in the serum lutein concentrations and MPOD levels at baseline between the groups. The increased serum lutein concentration and MPOD levels at 3 months were respectively, 89% and 38% in the free lutein group and 97% and 17% in the lutein esters group. The serum lutein concentrations in both groups and MPOD levels in the free lutein group increased significantly (p < 0.05) from baseline. No significant differences in serum lutein concentrations and MPOD levels were seen between the groups. Three months after supplementation ended, the serum lutein concentration decreased; the MPOD remained elevated in both groups. CONCLUSIONS: The serum lutein concentrations and MPOD levels increased significantly with either free lutein or lutein esters, and no significant differences were found between the two. Both were considered useful as lutein supplements.

Traditional Japanese herbal (kampo) medicines and treatment of ocular diseases: a review.

Herbal medicines have been used clinically in Eastern Asia, and traditional Japanese herbal (Kampo) formulas are approved as ethical drugs. The Kampo formulas are mixtures of the crude extracts of several herbs, each of which contains multiple components. Numerous investigators have reported that some herbal medicines are efficacious for treating several human diseases. We reviewed the literature on traditional herbal medicines and treatment of ocular diseases. Oral Orengedoku-to and Kakkon-to inhibit postoperative uveitis in humans. Oral Goshajinki-gan improved ocular surface disorders in patients with type 1 diabetes mellitus. Oral Hachimijio-gan increased retinal blood flow. Keishi-bukuryo-gan Sho might be associated with vitreoretinopathy in patients with type 2 diabetes mellitus. Oral Hachimijio-gan and Goshajinki-gan delayed lens opacification in rats and mice. Oral Sairei-to, Orengedoku-to, Senkanmeimoku-to, Scutellariae radix extract, Gardeniae fructus extract, topical Liguisticum wallichii rhizoma extract, and intravenous injection of tetramethylpyrazine, baicalin, baicalein, wogonin, and crocetin inhibited some forms of experimental uveitis in rabbits. Topical glycyrrhizinate improved allergic conjunctivitis in humans and rats. Oral crocetin improved eyestrain in humans. Oral berberine diminished experimental uveitis in rats. Baicalein, wogonin, berberine, and berberrubine inhibited in vitro expression of several cytokines in cultured retinal pigment epithelial cells. Some Kampo formulas are efficacious for treating several ocular diseases in humans and animals. Some herbal extracts and their components inhibit some forms of experimental uveitis.

Macular pigment density changes in Japanese individuals supplemented with lutein or zeaxanthin: quantification via resonance Raman spectrophotometry and autofluorescence imaging.

PURPOSE: Our purpose was to determine whether either lutein or zeaxanthin supplementation affects macular pigment concentration/optical density (MPOD) in healthy Japanese individuals. METHODS: Twenty-two healthy volunteers were randomized to either 10 mg of orally administered lutein or zeaxanthin daily for up to 3 months. MPOD levels were measured by resonance Raman spectrophotometry (RRS) and one-wavelength autofluorescence imaging (AFI) at baseline and 1, 2, and 3 months after the start of supplementation. RESULTS: MPOD levels measured with each method were correlated significantly at all time points. MPOD(RRS) and MPOD(AFI) levels increased >20 % from baseline at 2 and 3 months after lutein supplementation. By multiple regression analyses, the refractive error was correlated positively with MPOD(RRS) levels at baseline, whereas age and sex were not significant. In the lutein group, MPOD(RRS) levels significantly increased from baseline at all time points in individuals without high myopia exceeding -4 diopters, whereas the increase was not observed in individuals with high myopia. In the zeaxanthin group, MPOD(RRS) levels remained unchanged in those with and without high myopia. CONCLUSIONS: MPOD(RRS) and MPOD(AFI) levels correlated significantly with each other. In normal healthy Japanese individuals without high myopia, lutein supplementation increased MPOD levels within the fovea more effectively than did zeaxanthin.

Retinal risks of high-dose ornithine supplements: a review.

We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH(3) detoxification in the hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 µmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 µmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 µmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH(3) detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine.

Acceleration of age-related changes in the retina in alpha-tocopherol transfer protein null mice fed a Vitamin E-deficient diet.

PURPOSE: To assess the role of vitamin E (VE) in age-related changes in the retinal tissues by using a mouse model of severe VE deficiency. METHODS: Pups of alpha-tocopherol transfer protein null (a-TTP(-)(/)(-)) mice were fed a VE-deficient diet for 4 or 18 months (VE (-) group). Wild-type C57BL/6 mice were fed a 0.002% alpha-tocopherol-supplemented diet (VE (+) group). In various ocular tissues, the VE levels were measured by high-performance liquid chromatography; the fatty acid composition by gas chromatography (GC); and the hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels, which are biomarkers for lipid peroxidation, by GC-mass spectrometry. The retinal structure was assessed by light, electron, and fluorescence microscopy. RESULTS: The alpha-tocopherol level in the retinas obtained from 4-month-old VE (-) animals was 71-fold lower than that in the retinas obtained from the VE (+) group. In addition, gamma-tocopherol was not detected; thus, the VE (-) group demonstrated a more severe VE deficiency than ever reported. In this group, the concentration of n-3 polyunsaturated fatty acids decreased (0.3- to 0.9-fold), whereas that of other classes of fatty acids was unchanged or increased. At 18 months of age, the number of the outer nuclear layer (ONL) nuclei was observed to be 17% lower in the VE (-) than in the VE (+) group (P < 0.05). Electron microscopy revealed larger amounts of matrix between the ONL nuclei indicating the Müller cell hypertrophy, greatly expanded rod outer segment discs, and a larger number of inclusion bodies in the retinal pigment epithelium (RPE; P < 0.05) in the VE (-) group. Fluorescence microscopy revealed that the autofluorescence signal was increased in the RPE layer in this group. When the observations of the 18-month-old animals were compared to those of the 4-month-old animals, the hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels were found to be increased in the retina and RPE obtained from both the VE (-) and VE (+) groups; however, the age-related increases were more remarkable in the VE (-) group (2.6- to 43.5-fold) than in the VE (+) group (0.8- to 8.7-fold). CONCLUSIONS: The combined use of a-TTP(-)(/)(-) mice and a VE-deficient diet leads to a severe deficiency of VE, enhances lipid peroxidation in the retina, and accelerates degenerative damage of the retina with age.