ascorbic-acid and Retinal-Degeneration

Topics: Animals; Ascorbic Acid; Awards and Prizes; beta Carotene; Carotenoids; Disease Models, Animal; Humans; Light; Ophthalmology; Photoreceptor Cells; Retina; Retinal Degeneration; Societies, Medical

Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention.. The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy.. Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036).. Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.

Topics: Adult; Aged; Antioxidants; Antiviral Agents; Ascorbic Acid; Female; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Retinal Degeneration; Treatment Outcome

Retinal pigment epithelial (RPE) cell replacement therapy has provided promising outcomes in the treatment of retinal degenerative diseases (RDDs), but the resulting limited visual improvement has raised questions about graft survival and differentiation. Through combined treatment with vitamin C and valproic acid (together, VV), we activated human fetal RPE (fRPE) cells to become highly proliferative fetal RPE stem-like cells (fRPESCs). In this study, we report that SOX2 (SRY-box 2) activation contributed to mesenchymal-epithelial transition and elevated the retinal progenitor and mesenchymal stromal markers expressions of fRPESCs. These fRPESCs could differentiate into RPE cells, rod photoreceptors, and mesenchymal lineage progenies under defined conditions. Finally, fRPESCs were transplanted into the subretinal space of an RDD mouse model, and a photoreceptor rescue benefit was demonstrated. The RPE and rod photoreceptor differentiation of transplanted fRPESCs may account for the neural retinal recovery. This study establishes fRPESCs as a highly proliferative, multi-lineage differentiation potential (including RPE, rod photoreceptor, and mesenchymal lineage differentiation), mesenchymal-to-epithelial-transitioned retinal stem-like cell source for cell-based therapy of RDDs.

Topics: Animals; Ascorbic Acid; Biomarkers; Cell Differentiation; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fetal Stem Cells; Gene Expression Regulation; Humans; Mice; Retinal Degeneration; Retinal Pigment Epithelium; SOXB1 Transcription Factors; Treatment Outcome; Up-Regulation; Valproic Acid

Concerns have been raised about whether operating microscopes and endoillumination used during ophthalmic surgeries contribute to retinal damage. Despite the recognition that ascorbic acid (vitamin C) helps to protect the eye from light and the abundance of vitamin C in the retina, artificial aqueous humors used during surgery only contain the antioxidant glutathione. To test whether inclusion of antioxidants other than glutathione in surgical solutions might help to preserve retinal integrity, we studied the effects of vitamin C on acute toxicity in isolated rat retinas. Male Sprague-Dawley rats (PND 30+/-2) were sacrificed for retinal isolation. In the presence or absence of vitamin C (1 or 3 mM), retinas were exposed to 302 nm ultraviolet B (UVB) light for 1 h and were incubated for a total of 5 h at 30 degrees C. Retinal damage was assessed by morphological examination and biochemical assay measuring the amount of lactate dehydrogenase (LDH) released from injured cells. In control retinas, LDH release was significantly increased after UVB exposure. The presence of 1 mM vitamin C in the incubation media significantly reduced LDH release during the post-incubation period following UV exposure. No difference was found between 1 and 3 mM vitamin C. Microscopic examination revealed that disorganization in the outer nuclear layer after UVB exposure was markedly attenuated by administration of 1 mM vitamin C. Vitamin C (1 mM), a concentration found in the anterior chamber in humans, but not glutathione, prevented phototoxic injury following UV exposure. Although vitamin C itself cannot be used in intraocular irrigating solutions because of adverse interactions with iron released during bleeding, inclusion of antioxidants equivalent to vitamin C should be considered to help protect the retina from intraoperative light toxicity.

Topics: Animals; Ascorbic Acid; L-Lactate Dehydrogenase; Male; Models, Animal; Photoreceptor Cells, Vertebrate; Rats; Rats, Sprague-Dawley; Retinal Degeneration; Tissue Culture Techniques; Ultraviolet Rays; Vitamins

The injection of oxidative metabolites such as lipid peroxides (LPO) into the vitreous cavity led to tissue damage demonstrable by a dose-dependent increase in intravitreal and intralental LPO levels, which are expressed as thiobarbituric-acid-reactive substances (TBARS). This process was accompanied by an inflammatory response as indicated by the occurrence of leukocyte-derived myeloperoxidase (MPO) in the vitreous body. Intramuscular injections of vitamin E were very effective in reducing both TBARS and MPO activity, whereas vitamin C had a moderate effect on TBARS only. The injection of a combination of the two vitamins was no more effective than treatment with vitamin E alone.

Topics: Animals; Ascorbic Acid; Female; Lens, Crystalline; Lipid Peroxidation; Lipid Peroxides; Neutrophils; Peroxidase; Rabbits; Retinal Degeneration; Thiobarbituric Acid Reactive Substances; Vitamin E; Vitreous Body

In dark-reared albino rats, exposure to 2 or 3 hr of intense light interrupted by 2 hr dark periods resulted in extensive degeneration of photoreceptor cells and degeneration of the retinal pigment epithelium (RPE). Ascorbate (ie, vitamin C) administration prior to light exposure protected photoreceptors and the RPE from light damage. In the present study, ascorbate-treated and untreated rats were exposed to various cycles of intermittent light. Immediately after this light exposure, phagosome frequency in the RPE was morphologically evaluated in comparable 50 microns sections. In untreated rats, exposure to 2 or 3 hr of intermittent light resulted in a five- to sixfold increase in phagosome density compared to unexposed controls. In contrast, no increase in phagosome density was observed in ascorbate-treated rats. In these animals, under all lighting regimens, phagosome levels remained essentially identical to those in rats not exposed to light. After a single nondamaging light exposure, phagosome density remained at the level of dark controls in ascorbate-treated and untreated rats. These results indicate that phagosome frequency may serve as an index for light damage and that the protective effect of ascorbate may be linked to its capacity to prevent rod outer segment shedding and phagocytosis under intense light conditions.

Topics: Animals; Ascorbic Acid; Dark Adaptation; Light; Male; Phagocytosis; Phagosomes; Photoreceptor Cells; Pigment Epithelium of Eye; Rats; Rats, Inbred Strains; Retinal Degeneration; Rod Cell Outer Segment

To assess the protective effect of ascorbic acid in retinal light damage of rats, we have determined the uptake and retinal tissue distributions of its L- and D- stereoisomers following interperitoneal or intraocular injections. The effects of intense-intermittent light exposure and darkness on tissue ascorbate were compared by measuring its levels in retina and retinal pigment epithelial tissues at various times after administration. The protective effects of the two forms of ascorbate against retinal light damage were also compared by measuring rhodopsin levels 2 weeks after intense light exposure. After interperitoneal injection, both forms of ascorbic acid were higher in the retinal pigment epithelial-choroid-scleral complex (eye cup) than in the retina. Over a 2 hr post-injection period, L-ascorbate in the eye cup was 2 to 4 fold higher than normal (10-11 nmol); D-ascorbate levels were between 15 and 30 nmol. During the same period retinal L-ascorbate was just above normal (12-14 nmol), whereas less than 5 nmol of D-ascorbate was present. When ascorbate was given by the intraocular route the opposite effect was found. During the 2 hr post-injection period retinal L-ascorbate levels were 2 to 5 fold higher than normal; D-ascorbate was between 25 and 50 nmol/retina. Within 1 hr post-injection, L-ascorbate in the eye cup was near normal and D-ascorbate levels were 10 nmol or less. In uninjected rats perfused with normal saline, the endogenous L-ascorbate was distributed 55% in the retina with 9% and 36%, respectively, in the RPE-choroid and sclera. Ten-thirty min after interperitoneal peritoneal injection about 40% of the L-ascorbate was present in the retina with 17% and 44% in the RPE-choroid and sclera. Total ascorbate (L + D) levels in the same tissues of D- injected rats were similar to those found for rats given L-ascorbate. Following 7 hrs of darkness, tissue ascorbate levels in the injected rats decreased to approximately the same levels present in uninjected animals. For rats exposed to intense light average retinal ascorbate levels decreased further, while RPE-choroid and scleral levels were largely unchanged from the dark control levels. About 50% of the tissue ascorbate was present in the retina 10-30 min after intraocular injection. The RPE-choroid contained between 10 and 14% of the ascorbate, with 35-40% present in the sclera. Retinal ascorbate levels remained high in the injected eyes following 2.5 hrs of darkness, but decreased as a res

Topics: Animals; Ascorbic Acid; Chromatography, High Pressure Liquid; Dark Adaptation; Injections; Injections, Intraperitoneal; Light; Male; Rats; Rats, Inbred Strains; Retina; Retinal Degeneration; Rhodopsin; Stereoisomerism; Time Factors; Tissue Distribution

Topics: Animals; Ascorbic Acid; Biomechanical Phenomena; Docosahexaenoic Acids; Light; Lipids; Male; Photoreceptor Cells; Rats; Rats, Inbred Strains; Reference Values; Retinal Degeneration; Rhodopsin; Rod Cell Outer Segment

Topics: Animals; Ascorbic Acid; Biomechanical Phenomena; Dark Adaptation; Diet; DNA; Electrophysiology; Light; Periodicity; Rats; Retina; Retinal Degeneration

Ascorbic acid and glutathione were measured in retinas excised from normal rats reared in a cyclic light or dark environment and in dystrophic rats from the dark environment. Similar measurements were made on retinas from age matched rats exposed to intense visible light for periods of up to 24 hours. In other rats, ascorbic acid was given for various periods before exposure to intense light and the degree of photoreceptor cell death determined subsequently by rhodopsin measurements. In non-intense light treated rats ascorbate and glutathione were 12.1 nmol/retina at 20 days of age and 13.3 - 15.9 nmol/retina in 60 day old animals. In dystrophic rat retinas glutathione was 4-8% higher and ascorbate 10-20% higher than in normal dark reared rats. Although the levels of ascorbate and glutathione per retina increased during development, the molar ratios of the antioxidant materials to rhodopsin decreased by 36% and 60% in normal and dystrophic rats respectively. The levels of glutathione in young cyclic light or dark reared normals were unaffected by intense light exposure of either short (2-4 hrs) or long (24 hrs) duration. However, in both 20 and 40 day old dystrophic rats, intense light exposure resulted in a significant increase in retinal glutathione. In contrast to glutathione, retinal ascorbate decreased in normal rats exposed to intense light for 24 hrs, in an age and prior light environment dependent fashion. At ages greater than 20 days, normal rats exposed to light had significantly lower retinal ascorbate levels than their non-light exposed counterparts. The levels of ascorbate in 21-40 and 41-60 day old dark reared rat retinas were also significantly lower than in comparable intense light treated-cyclic light reared rats. In the youngest dystrophic rats whole eye ascorbate (retina, RPE, choroid and sclera) was 20-30% lower than in non-light treated rats, but in older mutant rats (41-60 day) light had no effect on the level of ascorbate in the retina. As determined by the level of rhodopsin remaining in the eye two weeks after 24 hrs light exposure, cyclic light reared rats lost 50-55% of their visual cells. However, cyclic light rats supplemented with ascorbic acid before intense light exposure lost only 30-35% of their visual cells.

Topics: Age Factors; Animals; Ascorbic Acid; Glutathione; Light; Rats; Retina; Retinal Degeneration

The changes in lipid peroxidation of the retina have been investigated during experimental degeneration induced by monoiodoacetic acid and oxygenous intoxication. The results obtained have shown that the development of experimental degeneration of the retina is accompanied by intensification of lipid peroxidation. Injection of vitamin E both before and after monoiodoacetic acid and oxygenous intoxication leads to suppression of lipid peroxidation.

Topics: Animals; Ascorbic Acid; Electroretinography; Ferrous Compounds; Guinea Pigs; In Vitro Techniques; Iodoacetates; Iodoacetic Acid; Lipid Peroxides; Oxygen; Rabbits; Retinal Degeneration; Vitamin E

Topics: Adrenal Cortex Hormones; Adult; Aged; Arterial Occlusive Diseases; Ascorbic Acid; Cerebrovascular Disorders; Child; Chorioretinitis; Edema; Female; Humans; Ketones; Male; Middle Aged; Retinal Artery; Retinal Degeneration; Retinal Diseases; Retinal Vessels; Rutin; Vitamin B Complex; Xanthines

Topics: Animals; Ascorbic Acid; Bilirubin; Cats; Hematoporphyrins; Hemoglobins; Hemorrhage; Hemosiderin; Humans; Hyaluronic Acid; Light; Microscopy, Electron; Porphyrins; Retinal Degeneration; Vitreous Body

Topics: Ascorbic Acid; Cholestanes; Chromatography; Retinal Degeneration; Vitamin A; Vitamin D; Vitamins

Topics: Ascorbic Acid; Bacteria; Carbohydrate Metabolism; Retinal Degeneration; Yeasts

Topics: Ascorbic Acid; Chromatography; Retinal Degeneration; Vitamins