Therapeutic Effects of Anti-Inflammatory and Anti-Oxidant Nutritional Supplementation in Retinal Ischemic Diseases.

Appropriate nutrients are essential for cellular function. Dietary components can alter the risk of systemic metabolic diseases, including cardiovascular diseases, cancer, diabetes, and obesity, and can also affect retinal diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. Dietary nutrients have been assessed for the prevention or treatment of retinal ischemic diseases and the diseases of aging. In this article, we review clinical and experimental evidence concerning the potential of some nutritional supplements to prevent or treat retinal ischemic diseases and provide further insights into the therapeutic effects of nutritional supplementation on retinopathies. We will review the roles of nutrients in preventing or protecting against retinal ischemic diseases.

Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal Diseases.

Fructus lycii (F. lycii) is an exotic "berry-type" fruit of the plant Lycium barbarum that is characterized by a complex mixture of bioactive compounds distinguished by their high antioxidant potential. F. lycii is used in traditional Chinese home cooking and in the Chinese Pharmacopeia as an aid to vision and longevity as well as a remedy for diabetes to balance "yin" and "yang" in the body for about two centuries. Although a myriad of bioactive compounds have been isolated from F. lycii, polysaccharides, carotenoids, flavonoids, and phenolics represent the key functional components of F. lycii. F. lycii has been shown to exhibit a wide range of biological activities in experimental settings including antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects. Despite its medicinal role dating back to the eighteenth century in the Far East and robust evidence of beneficial effects on ocular health and retinal diseases originating mainly from studies in animal models, the role of F. lycii in the clinical management of retinal diseases is yet to be established. This article comprehensively reviews the literature germane to F. lycii and retinal diseases with particular emphasis on age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa, which are commonly seen in clinical practice.

Suplementación nutricional con omega 3 en retina: relación entre volumen y concentración en productos comerciales / Nutritional supplements with omega 3 in retinal disease: Relationship between volume and concentration in commercial products

OBJETIVO: Comparar las características morfométricas y la concentración de ácido docosahexaenoico (DHA) y ácido eicosapentanoico (EPA) de los diferentes suplementos nutricionales con omega 3 disponibles en el mercado para las dolencias de la retina. MATERIAL Y MÉTODOS: Estudio doble ciego, con observador único, de una muestra de diferentes comprimidos de suplementación de omega 3 comercializados en España. Se estudió tanto la longitud del comprimido como la concentración de omega 3 en total y de DHA y EPA por separado, utilizando para ello la cantidad proporcionada por el fabricante y el volumen de la cápsula calculado a partir del desarrollo de una fórmula específica para ello. RESULTADOS: Se incluyeron un total de 10 suplementos nutricionales diferentes. La media de omega 3 total, DHA y EPA fue de 383,10 ± 160,90; 210,72 ± 93,3 y 112,34 ± 140,98 mg, respectivamente. El tamaño medio de las cápsulas fue de 14,77 ± 0,19×8,13 ± 0,09 mm. La cápsula de menor tamaño fue la de Oftan mácula omega(R) (Esteve, Barcelona, España). Brudymacula(R) (Brudylab, Barcelona, España) y Brudyretina 1.5 g(R) (Brudylab, Barcelona, España) son las cápsulas con mayor cantidad de DHA. Nutrof omega(R) (Laboratorios Thea, Barcelona, España) es la que presenta menor concentración de omega 3, DHA y EPA por cápsula. CONCLUSIÓN: Existen diferencias importantes en cuanto a tamaño, volumen, cantidad y concentración de omega 3 y sus derivados entre los diferentes preparados comerciales. Solo el conocimiento de las características de los suplementos nutricionales nos permitirá la personalización de su indicación a nuestros pacientes

OBJECTIVE: To analyse the morphometric characteristics and the concentration of (docosahexaenoic acid) DHA and eicosapentaenoic acid (EPA) of the different nutritional supplements with omega 3 available on the market for retinal disease. MATERIAL AND METHODS: A double-blind study was conducted with a single observer, of the different omega 3 supplementation tablets sample marketed in Spain. The length of the tablet, the concentration of omega 3 in total, as well as DHA and EPA were studied separately using the amount provided by the manufacturer and the volume of the capsule calculated from the development of a specific formula for it. RESULTS: A total of 10 different nutritional supplements were included. The mean of total omega 3, DHA and EPA was 383.10 ± 160.90, 210.72 ± 93.3, and 112.34 ± 140.98 mg, respectively. The mean size of the capsules was 14.77 ± 0.19×8.13 ± 0.09 mm The smallest sized capsule was that of Oftan macula omega(R) (Esteve, Barcelona, Spain). Brudymacula(R) (Brudylab, Barcelona, Spain) and Brudyretina 1.5 g(R) (Brudylab, Barcelona, Spain) tablets contained more DHA, with Nutrof omega(R) (Thea Laboratories, Barcelona, Spain) having the lowest concentration of omega 3, DHA and EPA, per tablet. CONCLUSION: There are significant differences in size, volume, quantity, and concentration of omega 3 and its derivatives, between different commercial preparations. Only the knowledge of the characteristics of the nutritional supplements will enable us to provide a more personalised indication of their use for our patients

Reduction of lipid accumulation rescues Bietti's crystalline dystrophy phenotypes.

Bietti's crystalline dystrophy (BCD) is an intractable and progressive chorioretinal degenerative disease caused by mutations in the CYP4V2 gene, resulting in blindness in most patients. Although we and others have shown that retinal pigment epithelium (RPE) cells are primarily impaired in patients with BCD, the underlying mechanisms of RPE cell damage are still unclear because we lack access to appropriate disease models and to lesion-affected cells from patients with BCD. Here, we generated human RPE cells from induced pluripotent stem cells (iPSCs) derived from patients with BCD carrying a CYP4V2 mutation and successfully established an in vitro model of BCD, i.e., BCD patient-specific iPSC-RPE cells. In this model, RPE cells showed degenerative changes of vacuolated cytoplasm similar to those in postmortem specimens from patients with BCD. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of autophagy flux, followed by cell death. Lipidomic analyses revealed the accumulation of glucosylceramide and free cholesterol in BCD-affected cells. Notably, we found that reducing free cholesterol by cyclodextrins or δ-tocopherol in RPE cells rescued BCD phenotypes, whereas glucosylceramide reduction did not affect the BCD phenotype. Our data provide evidence that reducing intracellular free cholesterol may have therapeutic efficacy in patients with BCD.

Use of propofol for short duration procedures in children with long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiencies.

The medication propofol, commonly used for anesthesia, has been avoided in patients with mitochondrial fatty acid oxidation disorders (FAODs) due to concerns that it contains long-chain fatty acids (LCFAs), and because of reports of severe side effects in some critically ill patients receiving high-dose propofol infusions that mimic some of the symptoms regularly found in FAOD patients. In this secondary analysis, we examined the outcomes of 8 children with long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency or trifunctional protein (TFP) deficiency who were repeatedly sedated for an electroretinogram (ERG) as part of a longitudinal study of the progression of chorioretinopathy commonly found in this population. A total of 39 sedated ERG procedures were completed using propofol for sedation. The propofol dosing, estimated total energy needs of the subject, and inpatient dietary intake recording were completed in 32 of these procedures. The LCFAs in the propofol provided approximately 1.0% of the average total daily energy needs. The sedation with propofol resulted in no adverse side effects and was safely used in this short duration procedure.

Lipemia retinalis: case report and review of the literature.

We report the case of a 12-week-old boy presenting with increased cholesterol and triglyceride levels. Examination revealed lipemia retinalis. Genetic evaluation demonstrated lipoprotein lipase deficiency. The patient was treated with dietary restrictions, which resulted in rapid clinical improvement.

Distinct retinal deficits in a zebrafish pyruvate dehydrogenase-deficient mutant.

Mutations in ubiquitously expressed metabolic genes often lead to CNS-specific effects, presumably because of the high metabolic demands of neurons. However, mutations in omnipresent metabolic pathways can conceivably also result in cell type-specific effects because of cell-specific requirements for intermediate products. One such example is the zebrafish noir mutant, which we found to be mutated in the pdhb gene, coding for the E1 beta subunit of the pyruvate dehydrogenase complex. This vision mutant is described as blind and was isolated because of its vision defect-related darker appearance. A detailed morphological, behavioral, and physiological analysis of the phenotype revealed an unexpected specific effect on the retina. Surprisingly, the cholinergic amacrine cells of the inner retina are affected earlier than the photoreceptors. This might be attributable to the inability of these cells to maintain production of their neurotransmitter acetylcholine. This is reflected in an earlier loss of motion vision, followed only later by a general loss of light perception. Since both characteristics of the phenotype are attributable to a loss of acetyl-CoA production by pyruvate dehydrogenase, we used a ketogenic diet to bypass this metabolic block and could indeed partially rescue vision and prolong survival of the larvae. The noir mutant provides a case for a systemic disease with ocular manifestation with a surprising specific effect on the retina given the ubiquitous requirement for the mutated gene.

Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy.

RATIONALE: Omega3 long-chain polyunsaturated fatty acids (omega3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing omega3-PUFA-dependent attenuation of angiogenesis. OBJECTIVE: This study aims to identify a major mechanism by which omega3-PUFAs attenuate retinal neovascularization. METHODS AND RESULTS: Administering omega3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)gamma almost completely abrogates this effect. Inhibition of PPARgamma also reverses the omega3-PUFA-induced reduction of retinal tumor necrosis factor-alpha, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor. CONCLUSIONS: These results identify a direct, PPARgamma-mediated effect of omega3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.

Lipemia retinalis in a 35-day-old infant with hyperlipoproteinemia: case report.

A rare case of hyperlipropoteinemia in a 35-day-old infant who presented not only high blood levels of cholesterol and triglycerides but also an ocular manifestation described as lipemia retinalis. The fundoscopic abnormality cleared as the levels of chilomicrons in plasma dropped. Lipemia retinalis is an important and reliable parameter of high levels of chilomicrons and triglycerides and should be considered as a significant clue while diagnosing.

Ophthalmologic abnormalities in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: presentation of a long-term survivor.

PURPOSE: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is one of the recently discovered defects of mitochondrial fatty acid beta-oxidation surprisingly associated with ophthalmologic abnormalities. The presentation of a long-term survivor may enlarge the clinical spectrum associated with this disorder. METHODS: A 12-year retrospective review of the clinical course of a 19-year-old long-term survivor was performed. The author concentrated on characteristic ophthalmologic measures: visual acuity, refraction, ophthalmoscopy, visual fields, and electroretinography. RESULTS: The author found a milder course than described in the literature, although very few case reports of long-term survivors have been published. The patient developed slower circumscribed atrophy of the choroid, retinal pigment epithelium, and retina. CONCLUSIONS: Because of therapeutic and prenatal diagnostic opportunities in LCHAD deficiency, it is important to recognize this severe disorder early in its course. This may lead to a milder course and better prognosis due to early dietary therapy.

Lipemia retinalis in a 35-day-old infant with hyperlipoproteinemia: case report / Lipemia retinalis em recém-nascido com 35 dias: relato de caso

A rare case of hyperlipropoteinemia in a 35-day-old infant who presented not only high blood levels of cholesterol and triglycerides but also an ocular manifestation described as lipemia retinalis. The fundoscopic abnormality cleared as the levels of chilomicrons in plasma dropped. Lipemia retinalis is an important and reliable parameter of high levels of chilomicrons and triglycerides and should be considered as a significant clue while diagnosing.

Caso raro de hiperlipoproteinemia em recém-nascido com 35 dias de idade. Identificados altos níveis de colesterol e triglicérides associados a manifestãção ocular descrita como lipemia retinalis. As alterações oculares mostraram melhora uma vez que os níveis séricos foram controlados. Lipemia retinalis é parâmetro confiável e importante a ser considerado como suspeita de alterações de colesterol e triglicérides em crianças e em adultos.

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency.

The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6omega-3) supplementation prevents the progression of the severe chorioretinopathy that develops in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Physical, biochemical, and ophthalmological evaluations, including electroretinogram (ERG) and visual acuity by evoked potential (VEP), were performed at baseline and annually following the initiation of 65-130 mg/day DHA supplementation and continued treatment with a low-fat diet. Fourteen children with LCHAD or TFP deficiency, 1-12 years of age at enrollment, were followed for 2-5 years. Three subjects with TFP beta-subunit mutations had normal appearance of the posterior pole of the ocular fundi at enrollment and no changes over the course of the study. Eleven subjects who were homozygote and heterozygote for the common mutation, c.1528G>C, had no change to severe progression of atrophy of the choroid and retina with time. Of these, four subjects had marked to severe chorioretinopathy associated with high levels of plasma hydroxyacylcarnitines and decreased color, night and/or central vision during the study. The plasma level of long-chain 3-hydroxyacylcarnitines, metabolites that accumulate as a result of LCHAD and TFP deficiency, was found to be negatively correlated with maximum ERG amplitude (Rmax) (p=0.0038, R2=0.62). In addition, subjects with sustained low plasma long-chain 3-hydroxyacylcarnitines maintained higher ERG amplitudes with time compared to subjects with chronically high 3-hydroxyacylcarnitines. Visual acuity, as determined with the VEP, appeared to increase with time on DHA supplementation (p=0.051) and there was a trend for a positive correlation with plasma DHA concentrations (p=0.075, R2=0.31). Thus, optimal dietary therapy as indicated by low plasma 3-hydroxyacylcarnitine and high plasma DHA concentrations was associated with retention of retinal function and visual acuity in children with LCHAD or TFP deficiency.

Mining MEDLINE for implicit links between dietary substances and diseases.

MOTIVATION: Text mining systems aim at knowledge discovery from text collections. This work presents our text mining algorithm and demonstrates its use to uncover information that could form the basis of new hypotheses. In particular, we use it to discover novel uses for Curcuma longa, a dietary substance, which is highly regarded for its therapeutic properties in Asia. RESULTS: Several disease were identified that offer novel research contexts for curcumin. We analyze select suggestions, such as retinal diseases, Crohn's disease and disorders related to the spinal cord. Our analysis suggests that there is strong evidence in favor of a beneficial role for curcumin in these diseases. The evidence is based on curcumin's influence on several genes, such as COX-2, TNF-alpha, JNK, p38 MAPK and TGF-beta. This research suggests that our discovery algorithm may be used to suggest novel uses for dietary and pharmacological substances. More generally, our text mining algorithm may be used to uncover information that potentially sheds new light on a given topic of interest. AVAILABILITY: Contact authors.

Long term dietary supplementation with zeaxanthin reduces photoreceptor death in light-damaged Japanese quail.

The purpose of these studies was to evaluate the effects of light damage on Japanese quail whose retinal carotenoids had been experimentally manipulated through altered diets. The birds were raised 6 months on a commercial turkey diet (T), on a custom carotenoid-deficient diet (C-) containing 90% less carotenoid than the T diet, or on Z+ diet [the C- diet supplemented with natural zeaxanthin (35mgkg(-1) food)]. Equal numbers of males and females on each diet were exposed to nine intervals (1hr on, 2hr off) of 3200lux cool white light, then placed in the dark for 14hr before tissue collection. One retina was immediately frozen for HPLC analysis; the other eye was immediately fixed and processed for microscopy. There were no significant differences in the retinal carotenoid concentrations in hatch-mates that were and were not exposed to light. Supplementation resulted in three- to four-fold increases in retinal zeaxanthin and no change in retinal lutein or alpha-tocopherol, but the C- diet did not reduce the retinal carotenoid concentration in C- birds below that in T birds. The light-exposed retinas had significant numbers of apoptotic photoreceptors and photoreceptor ghosts. The number of ghosts was negatively correlated with the number of dying photoreceptors (P<0.05), and with retinal concentrations of zeaxanthin, alpha-tocopherol or gamma-tocopherol (P<0.04, 0.02, 0.04, respectively), but not with lutein. The number of dying photoreceptors was positively correlated with alpha-tocopherol and the sum alpha-tocopherol plus zeaxanthin (P<0.1; P0.04). Photoreceptor death was semi-quantitatively scored, assuming that ghosts were formed by removal of apoptotic photoreceptors with nuclear condensation. Stepwise regression produced a good model (r(2)=0.67;P <0.0001) for predicting death scores from retinal concentrations of zeaxanthin (Standard Coefficient=-0.76) and lutein (Standard Coefficients=+0.43). Absence of lutein in gender-specific analyses suggests lutein served as surrogate marker for gender. Combined analysis of the C- and T birds also demonstrated that dying photoreceptors were negatively correlated with retinal zeaxanthin. These data confirm our previous report that retinal carotenoids prevent photoreceptor cell death, and provide the first direct evidence that retinal zeaxanthin protects photoreceptors from light-induced death.

Gyrate atrophy of the choroid and retina: further experience with long-term reduction of ornithine levels in children.

OBJECTIVE: To determine whether the long-term reduction of plasma ornithine levels by way of an arginine-restricted diet in patients with gyrate atrophy will slow the progression of this chorioretinal degeneration. DESIGN: Natural history study of 2 pairs of siblings with gyrate atrophy treated with an arginine-restricted diet. MAIN OUTCOME MEASURES: Fundus photography and electrophysical and psychophysical retinal function tests. RESULTS: After 16 to 17 years of receiving an arginine-restricted diet, the younger sibling in each pair, who was prescribed the diet at an earlier age than the older sibling, demonstrated a slower progression of lesions compared with the older sibling. CONCLUSIONS: If started at an early age, long-term substantial reduction of plasma ornithine levels may appreciably slow the progression of the chorioretinal lesions and, to a lesser extent, the progressive loss of retinal function in patients with gyrate atrophy.

Natural therapies for ocular disorders, part one: diseases of the retina.

Diseases of the retina are the leading causes of blindness throughout the world. Evidence points to potential benefit from nutritional and botanical interventions for the prevention and treatment of several of these conditions, including macular degeneration, diabetic retinopathy, retinopathy of the newborn, and retinitis pigmentosa. Epidemiological evidence points to the potential of antioxidant vitamins E and C, carotenoids, zinc, and selenium in the prevention and possible treatment of macular degeneration. In addition, dietary components such as red wine-high in important flavonoids-and fruits and vegetables high in carotenoids appear to offer some protection. While diabetic retinopathy can best be prevented by maintaining good blood sugar control, there are a number of nutrients and botanicals which may help prevent and treat retinopathy by inhibiting protein glycosylation, stabilizing collagen, decreasing capillary permeability, and providing important antioxidant effects. Extensive research on the use of vitamin E for the prevention of retrolental fibroplasia (retinopathy of the newborn), despite yielding promising results, has not resulted in incorporation of vitamin E into conventional standards of care protocols. Retinitis pigmentosa resembles the retinal damage seen in taurine-deficient cats. While patients with retinitis pigmentosa do not appear to be deficient in taurine, they appear to have faulty cellular uptake of this important amino acid. Disturbed utilization of vitamin A also appears to play a part in retinitis pigmentosa, and a subgroup of patients benefit from supplementation.

Lipaemia retinalis.

PURPOSE: To present a patient with the rare condition of lipaemia retinalis and discuss the clinical features of this condition and its association with elevated triglyceride levels. METHODS: Clinical evaluation of the patient, including fundus photographs before and after the initiation of a low fat diet, was undertaken. RESULTS: Lowering of serum triglyceride and cholesterol levels was associated with complete resolution of the clinical picture of lipaemia retinalis. CONCLUSIONS: Lipaemia retinalis is a rare condition that is related to markedly elevated triglyceride levels. Lowering triglycerides levels leads to resolution of the clinical picture of this disease.