Effects of caloric restriction on retinal aging and neurodegeneration.

Glaucoma is the most common neurodegenerative cause of irreversible blindness worldwide. Restricted caloric regimens are an attractive approach for delaying the progression of neurodegenerative diseases. Here we review the current literature on the effects of caloric restriction on retinal neurons, under physiological and pathological conditions. We focused on autophagy as one of the mechanisms modulated by restricted caloric regimens and involved in the death of retinal ganglion cells (RGCs) over the course of glaucoma.

Substances of Interest That Support Glaucoma Therapy.

Glaucoma is a multifactorial disease in which pro-apoptotic signals are directed to retinal ganglion cells. During this disease the conventional outflow pathway becomes malfunctioning. Aqueous humour builds up in the anterior chamber, leading to increased intraocular pressure. Both of these events are related to functional impairment. The knowledge of molecular mechanisms allows us to better understand the usefulness of substances that can support anti-glaucoma therapy. The goal of glaucoma therapy is not simply to lower intraocular pressure; it should also be to facilitate the survival of retinal ganglion cells, as these constitute the real target tissue in this disease, in which the visual pathway is progressively compromised. Indeed, an endothelial dysfunction syndrome affecting the endothelial cells of the trabecular meshwork occurs in both normal-tension glaucoma and high-tension glaucoma. Some substances, such as polyunsaturated fatty acids, can counteract the damage due to the molecular mechanisms - whether ischemic, oxidative, inflammatory or other - that underlie the pathogenesis of glaucoma. In this review, we consider some molecules, such as polyphenols, that can contribute, not only theoretically, to neuroprotection but which are also able to counteract the metabolic pathways that lead to glaucomatous damage. Ginkgo biloba extract, for instance, improves the blood supply to peripheral districts, including the optic nerve and retina and exerts a neuro-protective action by inhibiting apoptosis. Polyunsaturated fatty acids can protect the endothelium and polyphenols exert an anti-inflammatory action through the down-regulation of cytokines such as TNF-α and IL-6. All these substances can aid anti-glaucoma therapy by providing metabolic support for the cells involved in glaucomatous injury. Indeed, it is known that the food we eat is able to change our gene expression.

The relation between dietary intake and glaucoma: a systematic review.

PURPOSE: A common question of patients to their physician is what they can do themselves against glaucoma, except taking their daily medication. However, for ophthalmologists, it is often hard to give their patients an advice on their dietary intake. To help ophthalmologists in answering this question, an overview of the current scientific literature on the association of nutrients with glaucoma is presented. METHODS: A comprehensive systematic review was conducted in which articles published up to September 2017 were identified in PubMed and reference lists. Nutrients were categorized into minerals and trace elements, nutrition with antioxidative properties and omega-fatty acids. RESULTS: The literature search revealed a total of 407 articles of which a total of 46 met the inclusion criteria. Most of these articles studied the effect of nutrients on open-angle glaucoma. Many trace elements have been investigated in the literature, but the most interesting are selenium and iron (both may increase the risk of glaucoma). Investigated nutrients with antioxidative properties and omega-fatty acids included glutathione, nitric oxide, carotenoids, flavonoids, and omega-3 and omega-6 fatty acids. Of these, glutathione, nitric oxide, and flavonoids had a significant protective effect on glaucoma. CONCLUSION: Intake of selenium and iron may increase the risk of glaucoma, though, only few studies have been done on this topic. Nitric oxide present in other dark green leafy vegetables seems to have a beneficial effect on glaucoma. However, the evidence for an association of dietary intake with glaucoma is still not strong. More (longitudinal and randomized clinical trials) studies are required to make the presented findings clinically applicable.

Guía de estilos de vida y glaucoma (II). Dieta, suplementos, drogas, sueño, embarazo e hipertensión arterial / Lifestyles guide and glaucoma (II). Diet, supplements, drugs, sleep, pregnancy, and systemic hypertension

Objetivos: Establecer guías para aconsejar a los pacientes respecto a la relación entre dieta y hábitos de vida y glaucoma. Métodos: Revisión de los trabajos publicados sobre glaucoma y la dieta, la ingesta de suplementos, el consumo de drogas o el tabaco, el sueño, el embarazo y la hipertensión. Los trabajos fueron clasificados según el Oxford Center for Evidence-Based Medicine. Resultados: La evidencia sobre la relación entre la dieta o el uso de suplementos y la incidencia o la progresión del glaucoma es insuficiente para justificar una recomendación. Si bien algunos estudios en glaucoma de tensión normal sugieren que el Ginkgo biloba podría reducir la progresión, no permiten recomendar su uso generalizado. Los estudios sobre tabaco no demuestran claramente una relación entre consumo de tabaco e incidencia del glaucoma. La marihuana no es un tratamiento útil para el glaucoma. Los resultados sobre la relación entre la apnea del sueño y glaucoma son heterogéneos, pero sí parece conveniente que los pacientes con grado moderado o severo de apnea sean evaluados para descartar glaucoma. El embarazo no suele afectar al curso de la enfermedad, pero varios medicamentos hipotensores pueden ser nocivos para el feto. La hipotensión nocturna es un factor de riesgo de empeoramiento del glaucoma. Conclusiones: Ciertas costumbres, circunstancias o enfermedades pueden tener una influencia en la aparición o progresión del glaucoma. Es importante conocer la evidencia científica existente para poder aconsejar adecuadamente a los pacientes (AU)

To establish evidence based guidelines to advise patients on the relationship between habits, diet, certain circumstances, diseases and glaucoma. Methods: Review of all published articles on glaucoma and sports or other activities. The papers were classified according to the level of scientific evidence based on the Oxford Centre for Evidence-based Medicine classification. Results: The evidence on the relationship between diet or supplements and the incidence or progression of glaucoma is insufficient to make a general recommendation for glaucoma patients. Although some studies on normal tension glaucoma suggest that Gingko biloba could reduce glaucoma progression, the results do not allow a general recommendation for all these patients. Similarly, the evidence on the usefulness of vitamin supplements is not conclusive. The studies on smoking do not clearly demonstrate the relationship between this habit and incidence of glaucoma. Marihuana is not a useful treatment for glaucoma. Although the results on the relationship between sleep apnoea and glaucoma are heterogeneous, it is recommended that patients with moderate to intense apnoea are tested for glaucoma. Pregnancy does not influence the course of the disease, but several hypotensive drugs may be harmful for the foetus. Nocturnal systemic hypotension is a risk factor for glaucoma progression. Conclusions: Certain habits, circumstances, or diseases may have an influence on the onset or progression of glaucoma. It is important to have adequate information about the scientific evidence in the publications in order to properly advise patients (AU)

Rational Basis for Nutraceuticals in the Treatment of Glaucoma.

BACKGROUND: Glaucoma, the second leading cause of blindness worldwide, is a chronic optic neuropathy characterized by progressive retinal ganglion cell (RGC) axons degeneration and death. Primary open-angle glaucoma (OAG), the most common type, is often associated with increased intraocular pressure (IOP), however other factors have been recognized to partecipate to the patogenesis of the optic neuropathy. IOP-independent mechanisms that contribute to the glaucoma-related neurodegeneration include oxidative stress, excitotoxicity, neuroinflammation, and impaired ocular blood flow. The involvement of several and diverse factors is one of the reasons for the progression of glaucoma observed even under efficient IOP control with the currently available drugs. METHODS: Current research and online content related to the potential of nutritional supplements for limiting retinal damage and improving RGC survival is reviewed. RESULTS: Recent studies have suggested a link between dietary factors and glaucoma risk. Particularly, some nutrients have proven capable of lowering IOP, increase circulation to the optic nerve, modulate excitotoxicity and promote RGC survival. However, the lack of clinical trials limit their current therapeutic use. The appropriate use of nutraceuticals that may be able to modify the risk of glaucoma may provide insight into glaucoma pathogenesis and decrease the need for, and therefore the side effects from, conventional therapies. CONCLUSION: The effects of nutrients with anti-oxidant and neuroprotective properties are of great interest and nutraceuticals may offer some therapeutic potential although a further rigorous evaluation of nutraceuticals in the treatment of glaucoma is needed to determine their safety and efficacy.

The Ketogenic Diet: Making a Comeback.

Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.

[Influence of Luxury Foodstuffs on Glaucoma]. / Einfluss von Genussmitteln auf das Glaukom.

The term "luxury foodstuffs" refers to foods which are not consumed because of their nutritional value. Classic modern luxury foodstuffs are alcohol, caffeine-containing drinks, cocoa, sugar and tobacco. The following review article examines some of these modern luxury foodstuffs in detail, as well as their influence on glaucoma. Thus, small quantities of alcohol lower high intraocular pressure and have a positive influence on the blood circulation of the optic nerve. In addition, red wine polyphenols exert vasoprotective effects. In general, however, alcohol consumption appears to have no significant effect on the prevalence of glaucoma. The most important source of caffeine intake is coffee consumption. In some studies, coffee consumption caused no changes in intraocular pressure, while others reported a rise. A large study showed a connection between heavy coffee consumption and the risk of pseudoexfoliation glaucoma. Green and black teas are rich sources of flavonoids with antioxidant activity. In addition, a slight trend for lowering the intraocular pressure has been measured. As regards chocolate, flavonoid-rich dark chocolate should be favoured, due to its antioxidant activity. It lowers blood pressure and improves endothelium-dependent vascular relaxation. Excessive sugar consumption over many years can lead to increased body mass index (BMI) and type 2 diabetes. Many studies show a positive relationship between BMI and intraocular pressure. Some studies have identified significant correlations between type 2 diabetes and the risk of glaucoma. Smoking is a very widespread stimulant; it narrows the blood vessels and thus reduces the blood circulation of the optic nerve. Otherwise, studies on the role of smoking as a risk factor for glaucoma have been very inconsistent. Luxury foodstuffs may effect glaucoma and should be included in the medical history.

A focus on resveratrol and ocular problems, especially cataract: From chemistry to medical uses and clinical relevance.

Low vision and blindness are important health problems that affect millions of people throughout the world. The most common and important pathologies are diabetic retinopathy, age-related macular degeneration, glaucoma as well as cataracts. The latter consists of an opacification of the lens of the eye which impedes the passage of light and represents one of the most important causes of vision loss. Among the risk factors for cataract development, there are life-style factors such as the use of tobacco, abuse of alcohol and unhealthy diet. In light of this, dietary components that possess anti-oxidant activity, such as polyphenols for instance, can be considered good candidates for human studies in the prevention and or treatment of such diseases. Among dietary components, the antioxidant capacity of certain polyphenols is well known, and these could be good candidates. In this review we focus our attention on the current scientific literature regarding to the effects of resveratrol on cataracts and other ocular diseases, along with its potential mechanism/s of action. A large number of preclinical studies support the involvement of resveratrol in clinical trials for the prevention and treatment of eye diseases induced by oxidative stress and inflammation, such as age-related cataract.

¿Qué comer y qué beber en el glaucoma? Evidencias a partir de estudios en humanos / What to eat and drink in glaucoma? Evidence from human studies

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Antioxidants and vision health: facts and fiction.

A number of nutritional supplements containing antioxidants are advertised for better vision health. Do they benefit the average consumer? The literature was examined for the effectiveness of antioxidants for human eye health, and for the intricacies in collection of such evidence. The following diseases were considered: cataract, glaucoma, age-related macular degeneration (AMD), retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature indicates that antioxidant supplements plus lutein have a reasonable probability of retarding AMD. For glaucoma, such supplements were ineffectual in some studies but useful in others. In some studies, antioxidant rich fruits and vegetables were also useful for protection against glaucoma. For diabetic retinopathy, antioxidant supplements may have a small benefit, if any, but only as an adjunct to glycemic control. In very high-risk premature retinopathy and retinitis pigmentosa, antioxidant supplements may be beneficial but those with excess Vitamin E should be avoided. For cataract, there is no evidence for an advantage of such nutritional supplements. However, lubricant drops containing N-acetylcarnosine may be helpful in initial stages of the disease. For eye infections and other causes of uveitis, antioxidants have not been found useful. We recommend that a diet high in antioxidant rich foods should be developed as a habit from an early age. However, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments.

[The place of micronutrition in glaucoma management]. / Place de la micronutrition dans la prise en charge du glaucome.

The field of micronutrition is currently being developed in ophthalmology. As observed in cardiovascular diseases, age-related macular degeneration (AMD) and ocular surface diseases, and even glaucoma could benefit from dietary modifications. Among the different fundamental dietary elements, the role of lipids and essential fatty acids seems particularly interesting.

A novel perspective on natural therapeutic approaches in glaucoma therapy.

Glaucoma is becoming recognised as a condition for which not only elevated intraocular pressure (IOP), but also non-pressure-dependent risk factors, are responsible. Better knowledge of the pathogenesis has opened up new therapeutic approaches that are often referred to as non-IOP-lowering treatment. These new avenues of treatment, some of which are still under investigation, include agents that can improve vascular regulation and blood flow to the eye and reduce oxidative stress. Vascular regulation can be improved systemically with magnesium. Dark chocolate and omega-3-fatty acids can also improve blood flow regulation. Oxidative stress at mitochondrial level can be reduced by gingko. Polyphenolic flavonoids (tea, coffee and red wine), anthocyanosides, ubiquinone and melatonin have antioxidant properties, and heat-shock proteins can be induced naturally by the use of sauna baths. Future intensive studies on the effect of these compounds may open up a new therapeutic era in glaucoma.

Reversal of mutant myocilin non-secretion and cell killing: implications for glaucoma.

Glaucoma is a progressive blinding disease characterized by gradual loss of vision due to optic neuropathy and retinal ganglion cell death. Increased intraocular pressure is a common feature of glaucoma that is thought to arise from an increased resistance to outflow of aqueous humor through the trabecular meshwork. Mutations of the myocilin gene are one cause of autosomal dominant juvenile- and adult-onset primary open angle glaucoma, but the mechanism by which mutant myocilins cause disease is poorly understood. We have found that disease-causing myocilin mutants are misfolded, are highly aggregation-prone and accumulate in large aggregates in the endoplasmic reticulum (ER) of human embryonic kidney cells and differentiated primary human trabecular meshwork (HTM) cells. In HTM cells, Pro370Leu mutant myocilin is not secreted under normal culture conditions and prolonged expression results in abnormal cell morphology and cell killing. Culturing HTM cells at 30 degrees C, a condition known to facilitate protein folding, promotes secretion of mutant myocilin, normalizes cell morphology and reverses cell lethality. Our results indicate that myocilin-associated glaucoma is an ER storage disease and suggest a progression of events in which chronic expression of misfolded, non-secreted myocilin leads to HTM cell death, trabecular meshwork dysfunction and, ultimately, a dominant glaucoma phenotype. The beneficial effects of facilitating folding and secretion of mutant myocilin suggest a new type of treatment for this form of glaucoma.

The enhanced effect of the combination of cannasol with timolol and with pilocarpine on intraocular pressure - abstract

Cannasol ophthalmic drop is prepared from the non-psychoactive fraction of Cannabis sativa. The preparation contains 0.1 percent benzalconium chloride as a preservative. Letters Patent have been granted in Jamaica at this time for the eye drop. Timolol and pilocarpine are established eye drops used to treat glaucoma. When Cannasol and timolol are added together, irrespective of the order of combination, there is a precipitous and prolonged fall in the intraocular pressure, both in the dog and in the human. When Cannasol is combined with pilocarpine, the result is the same. Both timolol and pilocarpine produce spikes (rebound) in therapy which can be dangerous to the optic disc. These spikes are not seen when Cannasol is used on its own or used in combination as mentioned above. The enhanced effect with timolol is greater than with pilocarpine and this is to be expected. Timolol is a beeta-adrenoceptor antagonist, while Cannasol is an alpha-adrenoceptor antagonist, while Cannasol is an alpha-adrenoceptor stimulant, both acting to reduce tumour formation. Pilocarpine on the other hand constricts the pupil and widens the filtration angle, a mechanism quited different from that of Cannasol or timolol. This combined effect is now being used to advantage in patients with glaucoma resistant to conventional treatment and who might otherwise need surgery (AU)