Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

The Value of OCT and OCTA as Potential Biomarkers for Preclinical Alzheimer's Disease: A Review Study.

Preclinical Alzheimer's disease (AD) includes cognitively healthy subjects with at least one positive biomarker: reduction in cerebrospinal fluid Aß42 or visualization of cerebral amyloidosis by positron emission tomography imaging. The use of these biomarkers is expensive, invasive, and not always possible. It has been shown that the retinal changes measured by optical coherence tomography (OCT) and OCT-angiography (OCTA) could be biomarkers of AD. Diagnosis in early stages before irreversible AD neurological damage takes place is important for the development of new therapeutic interventions. In this review, we summarize the findings of different published studies using OCT and OCTA in participants with preclinical AD. To date, there have been few studies on this topic and they are methodologically very dissimilar. Moreover, these include only two longitudinal studies. For these reasons, it would be interesting to unify the methodology, make the inclusion criteria more rigorous, and conduct longer longitudinal studies to assess the evolution of these subjects. If the results were consistent across repeated studies with the same methodology, this could provide us with insight into the value of the retinal changes observed by OCT/OCTA as potential reliable, cost-effective, and noninvasive biomarkers of preclinical AD.

Searching for the Antioxidant, Anti-Inflammatory, and Neuroprotective Potential of Natural Food and Nutritional Supplements for Ocular Health in the Mediterranean Population.

Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received much attention as potential tools for managing chronic-degenerative ocular diseases. A systematic search of PubMed, Web of Science, hand-searched publications and historical archives were performed by the professionals involved in this study, to include peer-reviewed articles in which natural food, nutrient content, and its potential relationship with ocular health. Five ophthalmologists and two researchers collected the characteristics, quality and suitability of the above studies. Finally, 177 publications from 1983 to 2021 were enclosed, mainly related to natural food, Mediterranean diet (MedDiet) and nutraceutic supplementation. For the first time, original studies with broccoli and tigernut (chufa de Valencia) regarding the ocular surface dysfunction, macular degeneration, diabetic retinopathy and glaucoma were enclosed. These can add value to the diet, counteract nutritional defects, and help in the early stages, as well as in the course of ophthalmic pathologies. The main purpose of this review, enclosed in the Special Issue "Health Benefits and Nutritional Quality of Fruits, Nuts and Vegetables," is to identify directions for further research on the role of diet and nutrition in the eyes and vision, and the potential antioxidant, anti-inflammatory and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts), the Mediterranean Diet, and nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss. This review work was designed and carried out by a multidisciplinary group involved in ophthalmology and ophthalmic research and especially in nutritional ophthalmology.

Beneficial effects of saffron (Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases.

Saffron (Crocus sativus L.) has been traditionally used in food preparation and as a medicinal plant. It currently has numerous therapeutic properties attributed to it, such as protection against ischemia, as well as anticonvulsant, antidepressant, anxiolytic, hypolipidemic, anti-atherogenic, anti-hypertensive, antidiabetic, and anti-cancer properties. In addition, saffron has remarkable beneficial properties, such as anti-apoptotic, anti-inflammatory and antioxidant activities, due to its main metabolites, among which crocin and crocetin stand out. Furthermore, increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, both in experimental models and in clinical studies in patients. Currently, saffron supplementation is being tested for ocular neurodegenerative pathologies, such as diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration and glaucoma, among others, and shows beneficial effects. The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases. This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

Goniodysgenesis variability and activity of CYP1B1 genotypes in primary congenital glaucoma.

Mutations in the CYP1B1 gene are currently the main known genetic cause of primary congenital glaucoma (PCG), a leading cause of blindness in children. Here, we analyze for the first time the CYP1B1 genotype activity and the microscopic and clinical phenotypes in human PCG. Surgical pieces from trabeculectomy from patients with PCG (n = 5) and sclerocorneal rims (n = 3) from cadaver donors were processed for transmission electron microscopy. Patients were classified into three groups depending on goniodysgenesis severity, which was influenced by CYP1B1 enzymatic activity. The main histological changes observed in the outflow pathway of patients with PCG and mutations in CYP1B1 were: i) underdeveloped collector channels and the Schlemm's canal; ii) abnormal insertion of the ciliary muscle; iii) death of the trabecular endothelial cells. Our findings could be useful in improving treatment strategy of PCG associated with CYP1B1 mutations.

Morphologic differences observed by scanning electron microscopy according to the reason for pseudophakic IOL explantation.

PURPOSE: To compare variations in surface morphology, as studied by scanning electron microscopy (SEM), of explanted intraocular lenses (IOLs) concerning the cause leading to the explantation surgery. METHODS: In this prospective multicenter study, explanted IOLs were analyzed by SEM and energy-dispersive X-ray spectroscopy. The IOLs were explanted in the centers of the research group from 2006 to 2012. The primary procedure was phacoemulsification in all cases. RESULTS: The study evaluated 40 IOLs. The main causes for explantation were IOL dislocation, refractive error, and IOL opacification. Those explanted due to dislocation demonstrated calcifications in 8 lenses (50%), salt precipitates in 6 cases (37.5%), and erythrocytes and fibrosis/fibroblasts in 2 cases (12.5%). In the refractive error cases, the SEM showed proteins in 5 cases (45.5%) and salt precipitates in 4 lenses (36.4%). In IOL opacification, the findings were calcifications in 2 of the 3 lenses (66.6%) and proteins in 2 lenses (66.6%). CONCLUSIONS: A marked variation in surface changes was observed by SEM. Findings did not correlate with cause for explantation. Scanning electron microscopy is a useful tool that provides exclusive information regarding the IOL biotolerance and its interactions with surrounding tissues.

"Super p53" mice display retinal astroglial changes.

Tumour-suppressor genes, such as the p53 gene, produce proteins that inhibit cell division under adverse conditions, as in the case of DNA damage, radiation, hypoxia, or oxidative stress (OS). The p53 gene can arrest proliferation and trigger death by apoptosis subsequent to several factors. In astrocytes, p53 promotes cell-cycle arrest and is involved in oxidative stress-mediated astrocyte cell death. Increasingly, astrocytic p53 is proving fundamental in orchestrating neurodegenerative disease pathogenesis. In terms of ocular disease, p53 may play a role in hypoxia due to ischaemia and may be involved in the retinal response to oxidative stress (OS). We studied the influence of the p53 gene in the structural and quantitative characteristics of astrocytes in the retina. Adult mice of the C57BL/6 strain (12 months old) were distributed into two groups: 1) mice with two extra copies of p53 ("super p53"; n = 6) and 2) wild-type p53 age-matched control, as the control group (WT; n = 6). Retinas from each group were immunohistochemically processed to locate the glial fibrillary acidic protein (GFAP). GFAP+ astrocytes were manually counted and the mean area occupied for one astrocyte was quantified. Retinal-astrocyte distribution followed established patterns; however, morphological changes were seen through the retinas in relation to p53 availability. The mean GFAP+ area occupied by one astrocyte in "super p53" eyes was significantly higher (p<0.05; Student's t-test) than in the WT. In addition, astroglial density was significantly higher in the "super p53" retinas than in the WT ones, both in the whole-retina (p<0,01 Student's t-test) and in the intermediate and peripheral concentric areas of the retina (p<0.05 Student's t-test). This fact might improve the resistance of the retinal cells against OS and its downstream signalling pathways.

Distribution and organization of the nerve fiber and ganglion cells of the human choroid.

Antibodies to the 68, 160 and 200 kD of the neurofilament triplets were used to study the distribution and organization of neuronal structures in the human choroid. Choroidal axons were observed in the suprachoroid and vascular laminae but absent from the choriocapillary layer. Most axons were situated in the suprachoroid. In this layer, there were band-like bundles. The two thickest band-like bundles could constitute the long ciliary nerve, while the rest could constitute short ciliary nerves. These bundles ran through the suprachoroid, branching out on the suprachoroid and the vascular laminae until they reached the ciliary body. In the submacular area of the suprachoroid, the branches of the band-like bundles were so intermingled that they looked like a meshwork. In the vascular layer, the large vessels and their primary branches were accompanied by paravascular axons. Some paravascular axons penetrated the medium-caliber vessel layer and in the submacular area interwove to form a network parallel to the arteriole walls. In addition, perivascular axons were revealed by antibodies to neuropeptides. Choroidal ganglion cells were more numerous in the central choroid, specifically in a circumferential area corresponding to the entrance of the short posterior ciliary arteries and their primary branches, and in the vicinity of the submacular area. These cells presented bipolar and multipolar morphology. The high concentration of innervation in the central human choroid could be necessary to maintain strict blood flow in this zone; thus if required, these neuron structures could induce early vasodilation reflexes at the entrance of the choroidal blood vessels to increase the blood flow.