Nrf-2-dependent antioxidant and anti-inflammatory effects underlie the protective effect of esculeoside A against retinal damage in streptozotocin-induced diabetic rats.

Esculeoside A (ESA) is a tomato-derived glycoside with antioxidant and anti-inflammatory properties. The protective effect of ESA against diabetic retinopathy is not well-investigated and was the core objective of this study. In addition, we tested if such protection involves the activation of Nrf2 signaling. Type 1 diabetes mellitus (T1DM) was induced in adult Wistar male rats by an intraperitoneal injection of streptozotocin (65 mg/kg). Non-diabetic and T1DM rats were divided into two subgroup groups given either the vehicle or ESA (100 mg)/kg. An additional T1DM group was given ESA (100 mg/kg) and an Nrf2 inhibitor (2 mg/kg) (n=8 rats/group). Treatments continued for 12 weeks. In this study, according to the histological features, ESA improved the structure of ganglionic cells and increased the number of cells of the inner nuclear and plexiform layers in the retinas of T1DM rats. Concomitantly, it reduced the retina levels of malondialdehyde (lipid peroxides), vascular endothelial growth factor, interleukin-6, tumor necrosis factor-α, Bax, and caspase-3. In the retinas of the control and diabetic rats, ESA boosted the levels of total glutathione, superoxide dismutase, heme-oxygenase-1, and Bcl2, reduced the mRNA levels of REDD1, and enhanced cytoplasmic and nuclear levels of Nrf2. However, ESA failed to alter the mRNA levels of Nrf2 and keap1, protein levels of keap1, plasma glucose, plasma insulin, serum triglycerides, cholesterol, and LDL-c in both the control and T1DM rats. In conclusion, ESA alleviates retinopathy in T1DM rats by suppressing REDD1-associated degradation and inhibiting the Nrf2/antioxidant axis.

Maslinic Acid Protects against Streptozotocin-Induced Diabetic Retinopathy by Activating Nrf2 and Suppressing NF-κB.

This study tested the protective effect of maslinic acid (MA) against diabetic retinopathy (DR) in rats with type 1 diabetes mellitus (T1DM) and investigated possible mechanisms of action. DM was introduced by streptozotocin (STZ) (65 mg/kg, i.p.). Control and STZ (T1DM) were divided into 2 subgroups, which received either the vehicle or MA (80 mg/kg). Serum, pancreases, and retinas were collected for further use. MA significantly reduced fasting glucose levels in the control and T1DM rats but enhanced fasting insulin levels and partially increased the size of the islets of Langerhans and the number of ß-cells in T1DM rats. In addition, MA significantly improved the retina structure by preventing the reduction in the area between the inner and outer limiting membranes (ILM and OLM, respectively) and increasing the number of cells forming the ganglion cell layer (GCL), inner nuclear layer (INL), and outer nuclear layer (ONL). Associated with these effects, MA significantly reduced the total levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as the nuclear levels of NF-κB p65, mRNA levels of Bax, and protein levels of cleaved caspase-3 in the retinas of T1DM rats. However, MA significantly lowered levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but significantly increased the nuclear levels of Nrf2, protein levels of Bcl2, and total levels of superoxide dismutase (SOD) and reduced glutathione (GSH) in the retinas of the control and T1DM rats. In conclusion, MA prevents DR by antioxidant potential mediated by the activation of Nrf2.

Ultrastructural changes of extraocular muscles in strabismus patients.

Strabismus is an ocular disorder characterized by partial or complete inability to keep eye alignment. It represents a very common ocular problem at ophthalmology clinics worldwide. The current study aimed to show the most encountered ultrastructural changes in extraocular muscles (EOMs) collected from patients with different forms of strabismus. Nine specimens of EOMs were collected from five patients during strabismus correction surgery and processed for light and electron microscopy examinations. Histologically, skeletal muscle fibers in normal EOMs appeared tight and normally arranged with clear striations. In strabismic muscles, the fibers appeared disarranged, and atrophied, swollen and disintegrated in some situations. By transmission electron microscopy, normal EOMs were formed of skeletal muscle fibers with intact basal membrane and sarcolemma, tightly aligned myofibrils with well-arranged sarcomeres, Z line and H zone, and normally distributed mitochondria. On the other hand, strabismic EOMs revealed vacuolation and degeneration of myofibrils, accumulation of lipid droplets, subsarcolemmal inclusions and clustering of mitochondria. EOMs obtained from a Down syndrome patient with V-pattern infantile esotropia showed extensive vacuolation and disintegration of myofibrils, and extra- and intracellular deposition of collagen fibers. Interestingly, some skeletal muscle cells exhibited features of autophagic cell death with a trial of engulfing process by neighboring cells. In conclusion, our study traces some characteristic ultrastructural changes in strabismic EOMs, most notably, extensive vacuolation, clustering of mitochondria, degeneration of myofibrils and autophagic changes. These changes might be emphasized as possibly secondary to strabismus.

Radiation-induced damage to lacrimal glands: an ultrastructural study in Sprague Dawley rats.

Injury to lacrimal glands represents a major health problem after radiation therapy of the head and neck malignancies. Accordingly, this study aimed to investigate significant ultrastructural changes of lacrimal glands and some of their underlying mechanisms following the exposure to different fractionated doses of irradiation. In this study, 28 Sprague Dawley (SD) rats were assigned to four groups (seven rats each): Group I acted as control and received no irradiation. Groups II-IV received fractionated irradiation of 5 Gy (100 cGy/fraction daily for 5 days), 9 Gy (300 cGy/fraction daily for 3 days), and 20 Gy (one fraction), respectively. One month after the experiment, examination of lacrimal glands with transmission electron microscopy (TEM) demonstrated dose-dependent ultrastructural changes in the lacrimal acinar and intralobular ductal epithelial cells. In the acinar cells, there were swollen rough endoplasmic reticulum, irregularly shaped nuclei with chromatin condensation, mitochondrial damage, and retention of secretory granules. Intaralobular ductal epithelial cells showed loss of surface microvilli and damage to mitochondria. In addition to the potential direct effects of irradiation on lacrimal acinar and intralobular ductal epithelial cells, damage to blood vessels and nerve endings seemed to mediate some of the underlying mechanisms of these irradiation-induced ultrastructural changes. In conclusion, using TEM reveals that lacrimal gland is highly sensitive to even small doses of irradiation therapy; in addition, swelling of rough endoplasmic reticulum and aberrant nuclei are the most encountered structural changes. Damage to blood vessels and nerve endings might mediate some of the underlying mechanisms of irradiation-induced secondary injury in lacrimal glands.

Polymorphism rs10483727 in the SIX1/SIX6 Gene Locus Is a Risk Factor for Primary Open Angle Glaucoma in a Saudi Cohort.

AIMS: Variant rs10483727 in the SIX1/SIX6 locus has been significantly associated with primary open angle glaucoma (POAG) in multiple ethnic groups. We conducted a case-control study to investigate the association between this variant and POAG in a Saudi cohort. MATERIALS AND METHODS: Polymorphism rs10483727 was genotyped by using a TaqMan® assay in 186 subjects comprising 92 unrelated POAG cases and 94 controls all of Saudi origin. RESULTS: The "C" allele frequency was 0.33 and 0.45 among POAG cases and controls, respectively (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.38-0.89; p = 0.013), suggesting a protective effect; and the "T" allele was associated with increased susceptibility to POAG (OR = 1.7, 95% CI = 1.11-2.58; p = 0.013). Genotype distribution was also significantly associated with POAG (χ2 = 6.41, df = 2, p = 0.041). Endophenotype traits such as intraocular pressure and cup/disk ratio did not show any significant genotype distribution in POAG cases. A binary logistic regression analysis used to evaluate the effects of age, gender, and genotype on the likelihood of having POAG showed that genotype distribution (p = 0.012) significantly affected the disease outcome as compared with age (p = 0.055) and sex (p = 0.432). CONCLUSION: The "T" allele of the rs10483727 polymorphism is an independent significant risk factor for POAG in the Saudi population.

Polymorphism rs13334190 in zinc finger protein 469 (ZNF469) is not a risk factor for keratoconus in a Saudi cohort.

OBJECTIVE: Polymorphism rs13334190 in the zinc finger protein 469 gene has been suggested to predispose toward a "thin" cornea, which then becomes keratoconic or is directly pathogenic. Thus, we genotyped polymorphism rs13334190 in 127 unrelated keratoconus cases and 168 control subjects from Saudi Arabia using Taq-Man® assay. RESULTS: The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. A minor allele frequency of 0.068 was comparable to the aggregate rates ranging from 0.060 to 0.086 observed in other populations. Binary logistic regression analysis was performed to ascertain the effects of age, gender and genotype on the likelihood of having keratoconus. The analysis indicated that increased age was statistically significant (p = 0.000) and that females have a 2.19-fold increased risk (p = 0.018) of developing keratoconus. The genotype frequencies did not differ between the sporadic or familial keratoconus cases. Polymorphism rs13334190 is not an independent risk factor for keratoconus in the Saudi cohort.

Occupational ocular incidents in dentists: a multicentre study in southwestern Saudi Arabia.

BACKGROUND: Dental practitioners are at high risk of occupational ocular incidents during their daily work practice. The aim of this study was to assess the prevalence, pattern and determinants of ocular incidents and to establish the use of eye protection by dental staff in southwestern Saudi Arabia. METHODS: This multicentre cross-sectional study was conducted among dental practitioners working in private, military and Ministry of Health dental clinics in southwestern Saudi Arabia. A predesigned self-report questionnaire was used to elicit information on demographics, splash or foreign body ocular incidents, postincident practices and use of eye protection. RESULTS: Of the 233 dental practitioners examined, 29.6% and 51.1% reported ocular incidents as a result of foreign bodies and fluid splashing, respectively. The risk of ocular incidents as a result of fluid splashing was significantly higher in the absence of postgraduate qualification [odds ratio (OR) = 3.04, 95% confidence interval (95% CI): 1.70-5.43], poor compliance with wearing eye protection (OR = 2.52, 95% CI: 1.49-4.28) and long work hours (OR = 2.16, 95% CI: 1.17-3.96). The most frequent postexposure practice was to rinse eyes under running water (87.5%). Approximately 4.2% and 9.2% of dental practitioners reported incidents of ocular injury and infection, respectively, and 14% reported that they never wore any eye protection. CONCLUSION: Occupational ocular incidents as a result of splashing and foreign bodies are relatively common among dental practitioners in southwestern Saudi Arabia. The absence of postgraduate qualification, poor compliance with wearing eye protection and working long hours are predictors of ocular incidents. Awareness about eye safety is therefore considered mandatory for dental practitioners in southwestern Saudi Arabia. Also, dental clinic administrators should provide and promote the use of eye protection.

Causes of Phakic Implantable Collamer Lens Explantation/Exchange at King Khaled Eye Specialist Hospital.

PURPOSE: The purpose of this study is to evaluate the causes of phakic implantable collamer lens (ICL) explantation/exchange at an eye hospital in Saudi Arabia. MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent ICL implantation from 2007 to March 2014 and data were collected on cases that underwent ICL explantation. RESULTS: Of the 787 ICL implants, 30 implants (3.8% [95% confidence interval 2.6%; 5.3%]) were explanted. The causes of explantation included incorrect lens size (22), cataract (4), high residual astigmatism (2), rhegmatogenous retinal detachment (1), and intolerable glare (1). Corrective measures mainly included an exchange with an appropriately sized lens (9), ICL explantation (11), with phacoemulsification and posterior chamber intraocular lens implantation (6), or replacement with an ICL of correct power (2). CONCLUSION: Incorrect ICL size was the most common cause of ICL explantation. More accurate sizing methods for ICL are required to reduce the explantation/exchange rate.

Causes of elevated intraocular pressure following implantation of phakic intraocular lenses for myopia.

The purpose of this study is to present the causes and visual acuity outcomes in patients with elevated intraocular pressure (IOP) following implantable collamer lens (ICL) implantation. A chart review identified patients who developed high IOP at any postoperative examination and a minimum follow-up period of 3 months after ICL implantation. Data are reported out to 6 months postoperatively. Outcome measures included causes of elevated IOP, best-corrected visual acuity (BCVA) at last visit, number of glaucoma medications, other interventions, and glaucomatous damage. Elevated IOP occurred in 58 (10.8 %) of 534 eyes that received ICL. The mean age was 28 ± 7.2 years. The preoperative IOP was 16.3 ± 1.2 mmHg. Elevated IOP most commonly occurred on the first postoperative day (23/58 (39.7 %) eyes) due to retained viscoelastic. This was followed by steroid response in 22/58 (37.9 %) eyes at 2-4 weeks postoperatively. IOP elevation in 6 (10.3 %) eyes was related to high ICL vault and pupillary block, and in 4 (6.9 %) eyes due to synechial angle closure. At last visit, BCVA was 20/40 or better in 56/58 (96.6 %) eyes, and 5/58 (8.6 %) eyes remained on glaucoma medications due to persistent steroid response (2 eyes), synechial angle closure glaucoma (1 eye), and other causes (2 eyes). One eye showed glaucomatous damage. Two eyes with high vault and elevated IOP underwent ICL explantation. There is a moderate risk of transiently developing elevated IOP after ICL implantation. Thorough removal of viscoelastic and use of anti-glaucoma medications during steroid use will reduce the majority of cases with postoperative IOP elevation.