Neuroprotection in Glaucoma: Old and New Promising Treatments.

Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra- and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.

Age-related changes in the kinetics of human lenses: prevention of the cataract.

The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina and, by changing shape, it adjusts focal distance (accommodation). The three classes of structural proteins found in the lens are α, ß, and γ crystallins. These proteins make up more than 90% of the total dry mass of the eye lens. Other components which can be found are sugars, lipids, water, several antioxidants and low weight molecules. When ageing changes occur in the lens, it causes a gradual reduction in transparency, presbyopia and an increase in the scattering and aberration of light waves as well as a degradation of the optical quality of the eye. The main changes that occur with aging are: 1) reduced diffusion of water from the outside to the inside of the lens and from its cortical to its nuclear zone; 2) crystalline change due to the accumulation of high molecular weight aggregates and insoluble proteins; 3) production of advanced glycation end products (AGEs), lipid accumulation, reduction of reduced glutathione content and destruction of ascorbic acid. Even if effective strategies in preventing cataract onset are not already known, good results have been reached in some cases with oral administration of antioxidant substances such as caffeine, pyruvic acid, epigallocatechin gallate (EGCG), α-lipoic acid and ascorbic acid. Furthermore, methionine sulfoxide reductase A (MSRA) over expression could protect lens cells both in presence and in absence of oxidative stress-induced damage. Nevertheless, promising results have been obtained by reducing ultraviolet-induced oxidative damage.

Fascicular Visual Field Defects in Open-Angle Glaucoma: Evaluation with Microperimetry.

Purpose. Use of microperimetry (Mp-1), correlating with Humphrey perimetry (30-2 program), in patients affected by primary open-angle glaucoma (POAG) with perimetric defects, in order to obtain an evaluation of the accuracy of the results obtained by Mp-1. Materials and Methods. In this study 40 eyes of 25 patients affected by POAG with perimetric defects were included. All patients underwent microperimetry test by Nidek Mp-1 (NAVIS software version 1.7.2, Nidek Technologies). Mean sensitivity values expressed in decibel (dB) of all tested dots and mean values for each quadrant obtained by microperimetric test were correlated with corresponding quadrants obtained by static perimetry analysis. Data were analyzed by Pearson's correlation and Bland-Altman analysis. Results. Interpolated data showed that mean sensitivity values in all spots tested by Mp-1 (11.98 dB, SD 4.31) may be significantly correlated with mean total values obtained by Humphrey 30-2 perimetry (17.95, SD 4.32), with correlation coefficient of 0.556. Conclusions. Topographic visualization of the perimetric alteration by microperimetry allows retesting areas with reduced sensitivity which are topographically visualized and displayable on the ocular fundus examination, avoiding worsening of the functional defect by better modulation of the antiglaucoma therapy and therefore it allows better monitoring of the pathologic functional damage.

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.

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.

Acetazolamide-induced cilio-choroidal effusion after cataract surgery: unusual posterior involvement.

Idiosyncratic reactions to a large number of drugs have been reported to cause choroidal detachment and secondary angle-closure glaucoma (ACG). We report a case of bilateral acute ACG and peculiar choroidal effusion following administration of oral acetazolamide immediately after cataract surgery. Few cases of acute secondary ACG with choroidal effusion and anterior shift of the lens-iris diaphragm have been associated with acetazolamide compared with other sulfonamides. As far as we are aware, posterior involvement with retinal folds and papillary edema due to acetazolamide has not been described before.