Anti-inflammatory role of curcumin in retinal disorders (Review).

Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione], the main component of turmeric (Curcuma longa, a flowering plant of the ginger family, Zingiberaceae), is known to possess different pharmacological activities, particularly anti-inflammatory and antioxidant properties. Since an underlying inflammatory process exists in several ocular conditions, such as anterior uveitis, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), the aim of the present review was to summarize the pleiotropic effects exerted by this molecule, focusing in particular on its beneficial role in retinal diseases. The anti-inflammatory activity of curcumin has also been described in numerous systemic inflammatory pathologies and tumors. Specifically, the biological, pharmaceutical and nutraceutical properties of curcumin are associated with its ability to downregulate the expression of the following genes: IκBα, cyclooxygenase 2, prostaglandin E2, interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor-α. According to this finding, curcumin may be useful in the treatment of some retinal disorders. In DR, proliferative vitreoretinopathy and AMD, beneficial effects have been observed following treatment with curcumin, including slowing down of the inflammatory process. Despite the aforementioned evidence, the main disadvantage of this substance is that it possesses a low solubility, as well as poor oral bioavailability due to its reduced absorption, rapid metabolism and rapid elimination. Therefore, several curcumin analogues have been synthesized and tested over the years, in order to improve the possible obtainable therapeutic effects. The purpose of the present review was to identify new aspects that could guide future research on this important traditional medicine, which is a well-tolerated natural product, and is widely considered safe and economical.

Therapeutic potential of curcumin in major retinal pathologies.

PURPOSE: The retina is continually exposed to free radicals from its rich blood supply, numerous mitochondria, and photons of light which strike its surface. Most pathological processes that take place in the retina, such as inflammation, cell apoptosis, or angiogenesis, can hence involve free radicals directly or indirectly.  Since inflammatory and oxidative stress pathways underlie retinal pathology, compounds that address these factors are therefore natural choices for treatment. This review article summarizes and provides commentary on curcumin's therapeutic potential use in ophthalmology with principal focus on retinal dosorders. METHODS: Curcumin (diferuloylmethane) is a compound of the Indian spice turmeric (Curcuma longa) that has been found to be efficacious in preventing and treating a number of inflammatory diseases and neoplastic processes. Curcumin exerts anti-inflammatory, anti-tumor, antioxidant, and VEGF inhibition properties through modulation of numerous biochemical mediators. This makes curcumin particularly effective in retinal disorders. RESULTS: Curcumin has found a role in slowing, and in some cases even reversing, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, proliferative vitreoretinopathy, and retinal cancers. CONCLUSIONS: However, studies on curcumin's efficacy have been limited mostly to animal studies. Moreover, the biomedical potential of curcumin is not easy to use, given its low solubility and oral bioavailability-more attention therefore has been given to nanoparticles and liposomes.

Three episodes of non-arteritic posterior ischemic optic neuropathy in the same patient treated with intravenous prostaglandin E1.

Non-arteritic posterior ischemic optic neuropathy (NA-PION) is a disorder involving reduced blood flow to the retrobulbar portion of the optic nerve. This disorder usually develops acutely, and research has suggested that high-dose steroid therapy soon after the onset of visual loss can result in significant visual improvement. This treatment, however, is not universally successful. The addition of a potent vasodilator could help to restore ocular blood flow. This case report describes the use of prostaglandin E1 (PGE1), a powerful vasodilator of the microcirculation, to treat three separate episodes of NA-PION over five years in the same patient. A 68-year-old white male was first seen in June 2009 with NA-PION in the left eye, and the condition was treated with steroids and PGE1. The patient had a subsequent episode in July 2010 that was treated with steroids and PGE1 and another in May 2014 that was treated with PGE1 alone. Visual acuity improved from 4/10 to 11/10 in 2009, from 4/10 to 11/10 in 2010, and from 5/10 to 10/10 in 2014. No complications due to the use of PGE1 were noted. PGE1 should be considered as a treatment for NA-PION to immediately restore blood flow and potentially improve vision.

Biomolecular Modulation of Neurodegenerative Events during Ageing.

The objective is to assess the modulation of retinal and optic nerve degenerative events induced by the combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) in an animal model of ageing. For this study, 24 male Wistar-Harlan strain rats were left to age for up to 24 months. One group of rats was subjected to a diet supplemented with ALA and SOD for 8 weeks, while another group was used as a positive control and not subjected to any dietary treatment. To assess the cytoprotective effects of the antioxidants, a morphological analysis was carried out on sections of retina and optic nerve head, stained with haematoxylin-eosin, followed by an analysis of the modifications to nuclear DNA detected by the TUNEL technique. The lipid peroxidation assay was used to assess the damage induced by oxidative stress at cell membrane level. The molecules involved in apoptosis mediated by oxidative stress, such as caspase-3 and inducible nitric oxide synthase, were also assayed by immunolocalization and western blot. ALA and SOD are able to counteract senile neurodegenerative deterioration to the retina and optic nerve. Indeed, the combination of these antioxidant molecules can reduce oxidative stress levels and thus prevent both nuclear degradation and subsequent cell death.

Curcumin: therapeutical potential in ophthalmology.

Curcumin (diferuloylmethane) is the main curcuminoid of the popular Indian spice turmeric (Curcuma longa). In the last 50 years, in vitro and in vivo experiments supported the main role of polyphenols and curcumin for the prevention and treatment of many different inflammatory diseases and tumors.The anti-inflammatory, antioxidant, and antitumor properties of curcumin are due to different cellular mechanisms: this compound, in fact, produces different responses in different cell types. Unfortunately, because of its low solubility and oral bioavailability, the biomedical potential of curcumin is not easy to exploit; for this reason more attention has been given to nanoparticles and liposomes, which are able to improve curcumin's bioavailability. Pharmacologically, curcumin does not show any dose-limiting toxicity when it is administered at doses of up to 8 g/day for three months. It has been demonstrated that curcumin has beneficial effects on several ocular diseases, such as chronic anterior uveitis, diabetic retinopathy, glaucoma, age-related macular degeneration, and dry eye syndrome. The purpose of this review is to report what has so far been elucidated about curcumin properties and its potential use in ophthalmology.

Visual rehabilitation in patients with myopic maculopathy: our experience.

OBJECTIVE: To evaluate the efficacy of the MP-1 microperimeter (Nidek Technologies Srl, Padova, Italy) and Visual Pathfinder (LACE Inc) in improving visual function of patients with myopic maculopathy. DESIGN: Prospective, nonrandomized, interventional case series. PARTICIPANTS: Seventeen patients (34 eyes) between 36 and 58 years of age with myopic maculopathy and central retinal scotomas. METHODS: After a complete eye examination, all patients underwent 10 training sessions with MP-1 biofeedback (7 minutes) and Visual Pathfinder (3 minutes) for each eye once a week. Statistical analysis was performed with Student t test. The p values less than 0.05 were considered statistically significant. RESULTS: The mean best corrected visual acuity increased from 0.64 ± 0.22 to 0.38 ± 0.20 logMAR at the end of follow-up (p = 0.03); visual-evoked potential P100 amplitude increased from 3.54 ± 1.90 to 6.64 ± 2.91 µV at the end of follow-up (p = 0.04); average retinal sensitivity, calculated in the 12 degrees of the central retina, increased from 6.6 ± 2.6 to 14.6 ± 3.6 dB (p = 0.03). Fixation behaviour in the 2 degrees of the central retina increased from 45% ± 17% to 75% ± 23% (p = 0.04). The bivariate contour ellipse area (95%) increased from 10.34 ± 3.11 to 7.64 ± 2.71 square degrees (p = 0.04). CONCLUSIONS: The combination of acoustic biofeedback training with MP-1 and Visual Pathfinder offers a reasonable improvement of visual function in patients with myopic maculopathy. This method might be considered as a rehabilitative strategy as a "therapeutic option" in these patients for whom most treatments usually do not work.

Lipoic acid in animal models and clinical use in diabetic retinopathy.

INTRODUCTION: Oxidative stress, a consequence of excessive production of reactive oxygen species (ROS), is a factor in the development of many diseases, including diabetes and its complications. Alpha-lipoic acid (ALA), a natural thiol antioxidant, has been shown to have beneficial effects on oxidative stress parameters in various tissues. This article is an up-to-date review of current thinking regarding ALA and its use in providing antioxidant (AO) drug therapy for ocular dysfunction due to diabetic retinopathy (DR). AREAS COVERED: ALA prevents micro- and macro-vascular damage through normalized pathways downstream of mitochondrial overproduction of ROS, and preserves pericyte coverage of retinal capillaries. In addition, clinical studies suggest that oral administration of ALA can improve insulin sensitivity in patients with type-2 diabetes. Moreover, ALA treatment has been shown to suppress expression of vascular endothelial growth factor (VEGF), angiopoietin 2 and erythropoietin via blockade of superoxide formation. EXPERT OPINION: The diverse beneficial effects of ALA, many of which have only recently been uncovered, suggest that it acts by multiple mechanisms on oxidative stress parameters. Consequently, ALA supplementation is an achievable adjunct therapy to help prevent vision loss in diabetic patients. Finally, further research to better understand the mechanism of ALA will be useful for the development of more effective therapies in patients affected by DR.

New trends in visual rehabilitation with MP-1 microperimeter biofeedback: optic neural dysfunction.

The aim of this study was to evaluate the efficacy of visual rehabilitation with MP-1 microperimeter biofeedback in advanced optic neural dysfunction due to glaucoma, and to precisely characterize fixation stability and location in affected patients. Ten patients (18 eyes) with advanced glaucoma were submitted to a rehabilitation protocol that consisted of: a 25-item questionnaire (National Eye Institute Visual Functioning Que stionnaire); measurement of visual acuity; a reading speed test; microperimetry with fixation study, retinal sensitivity and the bivariate contour ellipse area (BCEA). The rehabilitation program consisted of 10 training sessions of 10 minutes per eye performed over a period of one week and was repeated at four months, eight months, and one year. Statistical analysis was performed using the Student's t-test and Spearman correlation; p values less than 0.05 were considered statistically significant. In 13 eyes fixation changed from unstable to relatively unstable while its location changed from predominantly eccentric to predominantly central. In five eyes, fixation changed from relatively unstable to stable with a change of location from poor central fixation to predominantly New trends in visual rehabilitation with MP-1 microperimeter biofeedback: optic neural dysfunction central fixation. Mean retinal sensitivity changed from 7.43±8.28 dB to 8.33±9.04 dB (p<0.05); the mean best corrected visual acuity was 0.98±0.66 logMAR at the baseline assessment, and 0.75±0.6 logMAR at the end of rehabilitation (p>0.05); reading speed improved from a mean value of 31.4±4.3 words/minute to 55.6±3.2 words/minute at the end of the training (p<0.05). The BCEA changed from 0.94±0.39 deg2 to 0.86±0.46 deg2 (p=0.76). Rehabilitation with MP-1 biofeedback in patients with advanced glaucoma is a useful means of improving these patients' fixation stability, reading speed and quality of life.