Antonia Pascarella

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 curcumins 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.

Monoamine oxidase enzymes and oxidative stress in the rat optic nerve: age-related changes

In this study, age‐related changes in the monoamine oxidases (MAO) were studied in the optic nerve (ON) of both young and aged male rats. The aim of the study was to assess the role of MAO in age‐related changes in the rat ON and explain the mechanisms of neuroprotection mediated by MAO‐B‐specific inhibitors. Fifteen three month old and fifteen 26 month old Sprague–Dawley rats were used. The animals were killed by terminal anaesthesia. Staining of MAO, quantitative analysis of images, biochemical assays and statistical analysis of data were carried out. Samples of the ON were washed in water, fixed in Bowen fluid, dehydrated and embedded in Entellan. Histological sections were stained for MAO‐enzymatic activities. The specificity of the reaction was evaluated by incubating control sections in a medium either without substrate or without dye. The quantitative analysis of images was carried out at the same magnification and the same lighting using a Zeiss photomicroscope. The histochemical findings were compared with the biochemical results. After enzymatic staining, MAO could be demonstrated in the ON fibres of both young and aged animals; however, MAO were increased in the nerve fibres of the elderly rats. These morphological findings were confirmed biochemically. The possibility that age‐related changes in MAO levels may be attributed to impaired energy production mechanisms and/or represent the consequence of reduced energy needs is discussed.

Role of Protease-Inhibitors in Ocular Diseases.

It has been demonstrated that the balance between proteases and protease-inhibitors system plays a key role in maintaining cellular and tissue homeostasis. Indeed, its alteration has been involved in many ocular and systemic diseases. In particular, research has focused on keratoconus, corneal wounds and ulcers, keratitis, endophthalmitis, age-related macular degeneration, Sorsby fundus dystrophy, loss of nerve cells and photoreceptors during optic neuritis both in vivo and in vitro models. Protease-inhibitors have been extensively studied, rather than proteases, because they may represent a therapeutic approach for some ocular diseases. The protease-inhibitors mainly involved in the onset of the above-mentioned ocular pathologies are: α2-macroglobulin, α1-proteinase inhibitor (α1-PI), metalloproteinase inhibitor (TIMP), maspin, SERPINA3K, SERPINB13, secretory leukocyte protease inhibitor (SLPI), and calpeptin. This review is focused on the several characteristics of dysregulation of this system and, particularly, on a possible role of proteases and protease-inhibitors in molecular remodeling that may lead to some ocular diseases. Recently, researchers have even hypothesized a possible therapeutic effect of the protease-inhibitors in the treatment of injured eye in animal models.

DEHP effects on retinal vessels in newborn rats: a qualitative and quantitative analysis.

Di-(2-ethylhexyl)-phthalate (DEHP), employed in polyvinyl chloride fabrication and released by endotracheal tubes, is known to cause alterations to several mammalian tissues, markedly in immature animals. The high incidence and severity of bronchopulmonary dysplasia and retinopathy in preterm babies submitted to endotracheal intubation prompted us to investigate the effects of DEHP in lung and retina perinatal development. We previously demonstrated that in rats delivered and breast-fed by DEHP-treated mothers lung alveolarisation is severely impaired. In the present research, the maturation of retinal vessels was studied in (a) flat-mounted retinas obtained after intracardiac injection of FITC-conjugated dextran, (b) flat-mounted retinas incubated with FITC-conjugated Bandeira simplicifolia isolectin B4, marker of vascular endothelial cells, and (c) eyecup sections incubated with biotinylated IB4 and revealed by ABC. DEHP-induced vascular alterations mainly affected the superficial plexus, where the radial vessels showed non-perfused as well as remarkably dilated and branched segments, capillary net appeared coarsely arranged and locally absent; periarteriolar capillary-free regions were still found in 14-day-old animals. This extensive vascular remodelling and generally the high responsiveness to DEHP shown by the immature rat retina confirm previous hypothesis that the phthalate released by PVC medical devices remarkably affects perinatal development of several tissues in different body districts.

Modulatory effects of 1,25-dihydroxyvitamin D3 on eye disorders: A critical review

ABSTRACT Many studies have shown that the presence of 1,25-dihydroxyvitamin D3 in the eye is able to modulate inflammatory responses. In fact, it has been demonstrated that topical administration of vitamin D3 inhibits Langerhans cells migration from the central cornea, corneal neovascularization, and production of cytokines (i.e., interleukin-1-6-8) in experimental animals. Moreover, both in vitro and in vivo studies have demonstrated that vitamin D is a potent inhibitor of retinal neovascularization. It has been shown that calcitriol, the biologically active form of vitamin D, inhibits angiogenesis both in cultured endothelial cells and in retinas from guinea pigs with retinoblastoma or oxygen-induced ischemic retinopathy. In addition, it seems that this compound is able to prevent the progression from early to neovascular age-related macular degeneration (AMD) and, at the same time, to down-regulate the characteristic inflammatory cascade at the retinal pigment epithelium–choroid interface due to its anti-inflammatory and immunomodulatory capabilities. Furthermore, 1,25-dihydroxyvitamin D3 and its analogue, 2-methylene-19-nor-1,25-dihydroxyvitamin D3, are able to modulate intraocular pressure (IOP) through gene expression. Several studies have suggested a role in glaucoma and diabetic retinopathy therapies for vitamin D3. In conclusion, this review summarizes our current knowledge on the potential use of vitamin D3 in the protection and treatment of ocular diseases in ophthalmology.