Construction of a screening system for lipid-derived radical inhibitors and validation of hit compounds to target retinal and cerebrovascular diseases.

Recent studies have highlighted the indispensable role of oxidized lipids in inflammatory responses, cell death, and disease pathogenesis. Consequently, inhibitors targeting oxidized lipids, particularly lipid-derived radicals critical in lipid peroxidation, which are known as radical-trapping antioxidants (RTAs), have been actively pursued. We focused our investigation on nitroxide compounds that have rapid second-order reaction rate constants for reaction with lipid-derived radicals. A novel screening system was developed by employing competitive reactions between library compounds and a newly developed profluorescence nitroxide probe with lipid-derived radicals to identify RTA compounds. A PubMed search of the top hit compounds revealed their wide application as repositioned drugs. Notably, the inhibitory efficacy of methyldopa, selected from these compounds, against retinal damage and bilateral common carotid artery stenosis was confirmed in animal models. These findings underscore the efficacy of our screening system and suggest that it is an effective approach for the discovery of RTA compounds.

Comparison of Schlemm's Canal Morphology Parameters Between Propensity Score-Matched Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Purpose: This study aimed to histologically compare the status of Schlemm's canal (SC) and Schlemm's canal endothelial (SCE) cells between trabeculectomy specimens from patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods: A total of 182 eyes from 152 patients with POAG and 138 eyes from 116 patients with EXG underwent immunohistochemical staining for thrombomodulin. Equal numbers of cases were selected from both groups using propensity score matching. The following parameters were evaluated: total SC length, staining positive and negative SC length (PSC and NSC, respectively), opened and closed SC length, staining positive and opened SC length, staining positive and closed SC length, staining negative and opened SC length (NOSC), and staining negative and closed SC length. Results: After matching for age and gender, 87 cases were selected in each group. The EXG group had significantly higher preoperative IOP and medication scores. PSC was significantly longer in the POAG group, while NSC and NOSC were longer in the EXG group. Multiple regression analysis of these 174 cases revealed that PSC was significantly shorter in the EXG group. After matching for age, gender, preoperative IOP, and medication score, 64 cases were selected in each group, and NOSC was significantly longer in the EXG group. Conclusions: These findings suggest that in EXG, SCE loss occurs independently of background factors such as aging and medication use. The loss of SCE may have a more critical impact on IOP elevation in EXG compared to POAG.

Exploring the Pressure Characteristics of the PRESERFLO MicroShunt in In Vitro Studies and Effects of Sclera on Device Performance.

This study aims to investigate the pressure characteristics of the PRESERFLO MicroShunt, a microinvasive glaucoma device, using an in vitro setup. Additionally, the study explores the impact of the scleral tissue surrounding the device on its pressure and lumen area. Ten PRESERFLO MicroShunts were subjected to an in vitro experimental setup. A constant flow of physiological saline was maintained at 2 µL/min using an infusion syringe pump. The PRESERFLO was connected to a pressure transducer via a 23 G needle. Pressure characteristics were measured under three different conditions: without sclera [sclera (-)], passing through sclera at a 90° angle (sclera 90°), and passing through sclera at a 30° angle (sclera 30°). The lumen area of the device was measured using microscopic observation. We observed peak and trough pressures in this experimental setting; the peak pressure (6.76 mmHg) was significantly higher than the trough pressure of 4.74 mmHg (p = 0.0020) in the sclera (-) condition. Compared to sclera (-), the peak pressures were significantly higher in the sclera 90° (7.81 mmHg, p = 0.0020) and the sclera 30° (7.96 mmHg, p = 0.0039) conditions. Additionally, compared to sclera (-), the trough pressure was significantly higher in the sclera 90° (6.25 mmHg, p = 0.0039) and the sclera 30° (5.76 mmHg, p = 0.037) conditions. The lumen area was significantly smaller in the sclera 90° condition (3515 µm2) than the sclera (-) condition (3927 µm2, p = 0.0078). The study found that when the distal end of PRESERFLO MicroShunt was free and in air, it exhibited both peak and trough pressures. The presence of scleral tissue surrounding the PRESERFLO MicroShunt affects its lumen area and pressure characteristics. Understanding these effects can provide valuable insights into the device's performance.

Assessing the safety of new germicidal far-UVC technologies.

The COVID-19 pandemic underscored the crucial importance of enhanced indoor air quality control measures to mitigate the spread of respiratory pathogens. Far-UVC is a type of germicidal ultraviolet technology, with wavelengths between 200 and 235 nm, that has emerged as a highly promising approach for indoor air disinfection. Due to its enhanced safety compared to conventional 254 nm upper-room germicidal systems, far-UVC allows for whole-room direct exposure of occupied spaces, potentially offering greater efficacy, since the total room air is constantly treated. While current evidence supports using far-UVC systems within existing guidelines, understanding the upper safety limit is critical to maximizing its effectiveness, particularly for the acute phase of a pandemic or epidemic when greater protection may be needed. This review article summarizes the substantial present knowledge on far-UVC safety regarding skin and eye exposure and highlights research priorities to discern the maximum exposure levels that avoid adverse effects. We advocate for comprehensive safety studies that explore potential mechanisms of harm, generate action spectra for crucial biological effects and conduct high-dose, long-term exposure trials. Such rigorous scientific investigation will be key to determining safe and effective levels for far-UVC deployment in indoor environments, contributing significantly to future pandemic preparedness and response.

A case of two connected stents deployed during iStent inject W surgery.

BACKGROUND: We report a case with two connected stents ejected simultaneously during an iStent inject W surgery, a modified second-generation iStent Trabecular Micro-Bypass System. CASE PRESENTATION: A 57-year-old woman with primary open-angle glaucoma underwent a combined cataract and iStent inject W surgery in her left eye. After the trabecular meshwork/Schlemm's canal was pierced by the trocar of injector, the delivery button was pressed a first time, but the stent was not ejected. After the button was pressed a second time, connected two stents were ejected. After removing the dislocated stents from the anterior chamber, two stents were implanted into the desired places using another injector. Except for mild hyphema, no postoperative complication occurred. Stereomicroscopic observation showed that the two stents were connected by a broken trocar shaft. An X-ray showed that the trocar shaft was broken at the part referred to as the "sprayed trocar". Scanning electron microscopy showed that the surface features of the broken trocar and trocar tip represented tensile failure. CONCLUSIONS: Although rare, considering that the damage was seen at the structurally weak part (i.e., sprayed trocar), the same phenomenon can happen. For patient safety, surgeons are recommended to inspect the device when the deployment of either the first or second stent is unsuccessful during the iStent inject surgery.

Flow Pressure Characteristics of the Ahmed Glaucoma Valve and Possible Effect of Entrapped Air in the Tube.

Purpose: The purpose of this study was to assess the pressure characteristics of the Ahmed Glaucoma Valve (AGV) and possible effects of air trapped in the tube. Method: Physiologic saline was pumped through 17 AGVs using a syringe infusion pump, and the flow pressure was measured by a set of pressure transducers. During the infusion at a rate of 2 µL/minute, the pressure measurement was repeated twice in each AGV to determine the repriming pressures with/without air (1 µL) in the tube. Results: After a pressure surge occurred during the initial priming, the pressure decreased suddenly and then became constant. The repriming pressure, determined as the peak pressure before valve opening, was significantly (P < 0.0001, paired t-test) higher with air (26.5 ± 6.8 mm Hg) than without air (12.1 ± 3.8 mm Hg), whereas the constant pressures after repriming was equivalent between with (10.6 ± 3.7 mm Hg) and without (10.4 ± 2.9 mm Hg) air conditions (P = 0.68). Conclusions: Air in the AGV tube causes increased repriming pressure of about two-fold compared to repriming without air. This pressure increment caused by air in the capillary-sized tube might occur because of the effects of viscosity pressure and capillary pressure. Translational Relevance: To ensure stable surgical results, surgeons are advised to not allow air to remain in the tube. Pars plana tube insertion of the AGV combined with gas tamponade surgery may result in higher-than-expected intraocular pressure. Conversely, injection of air/gas can avoid postoperative hypotony when the AGV is implanted in eyes with a high risk of hypotony.

Linear association between aging and decreased blood thiol antioxidant activity in patients with cataract.

We comprehensively assessed the roles of systemic redox markers by including both prooxidant and antioxidant markers in 121 Japanese subjects (mean ±â€…SD age, 70 ±â€…11 years; 38 men) with no ocular pathology except age-related cataract. Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured using the diacron reactive oxygen metabolite (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free-radical analyzer. Univariate analyses suggested that older age, higher pulse rate, worse best-corrected visual acuity (BCVA), higher intraocular pressure, and higher cataract grade were associated with a lower SH level. Scatterplots revealed virtually linear associations between age and the SH level (estimate, -4.4 µM/year). Multivariate analyses suggested that older age, higher systolic blood pressure, and worse BCVA were associated with a lower SH level. Neither the univariate nor multivariate analyses, except between female sex and higher dROM level, were associated with the dROM or BAP level. A lower serum SH level was the driver of aging itself and age-related decline in VA due to cataract. The serum SH level may be an excellent predictor of aging status in each subject.

Safety Evaluation of Far-UV-C Irradiation to Epithelial Basal Cells in the Corneal Limbus.

Basal cells in the corneal limbus play an important role in the turnover cycle because they are the source of all cells that constitute the corneal epithelium. We examined the penetration depth of ultraviolet (UV) light in the corneal limbus and assessed the safety of Far-UV-C on stem cells in the basal area of the corneal limbus. Rats were irradiated with UV at peaks of 207, 222, 235, 254 and 311 nm while under anesthesia. The UV penetration depth in the rat corneal limbal epithelium was wavelength dependent: 311 nm UV-B and 254 nm UV-C reached the basal cells of the epithelium, and 235 nm radiation reached the middle area; however, 207 and 222 nm UV-C reached only the superficial layer of the epithelium. Porcine cornea, which is similar to the human eye in size and structure, were irradiated with 222 and 254 nm UV-C. As in rats, 222 nm UV-C reached only the superficial layer of the porcine corneal limbal epithelium. These results indicate that Far-UV-C, such as radiation of wavelengths of 207 and 222 nm, could not reach corneal epithelial stem cells, i.e. the cells remained intact. It is unlikely that the turnover of the corneal epithelium is obstructed or disrupted by exposure to Far-UV-C.

One-year Ocular Safety Observation of Workers and Estimations of Microorganism Inactivation Efficacy in the Room Irradiated with 222-nm Far Ultraviolet-C Lamps.

Two krypton-chloride germicidal excimer lamp units (Care222 TRT-104C11-UI-U3, USHIO Inc.) were installed in the examination room of an ophthalmology department. The irradiation dose was set not to exceed the former (i.e., before 2022) threshold limit value (TLV) (22 mJ cm-2 /8 h) recommended by the ACGIH. Section 1: The eyes and lids of the six ophthalmologists (5 wore glasses for myopic correction) who worked in the room for a mean stay of 6.7 h week-1 were prospectively observed for 12 months. Slitlamp examinations revealed neither acute adverse events such as corneal erosion, conjunctival hyperemia, and lid skin erythema nor chronic adverse events such as pterygium, cataract, or lid tumor. The visual acuity, refractive error, and corneal endothelial cell density remained unchanged during the study. Section 2: The irradiation of samples placed on the table or floor using the same fixtures in the room (5-7.5 mJ cm-2 ) was associated with >99% inhibition of φX174 phage and >90% inhibition of Staphylococcus aureus. In conclusion, no acute or chronic health effects in human participants was observed in a clinical setting of full-room ultraviolet germicidal irradiation by 222-nm lamp units, and high efficacy in deactivation of microorganisms was determined in the same setting.

Positive Association between Aqueous Humor Hydroxylinoleate Levels and Intraocular Pressure.

We previously proposed the total assessment of hydroxylinoleates (HODEs) by LC-MS/MS after saponification and reduction of the biologic samples as biomarkers to investigate pathogenesis, disease progression, and prognosis. In this study, HODE levels were estimated in aqueous humor (AH) samples from 63 eyes (41 Japanese subjects; 15 men; mean age, 77.3 ± 6.8 years) with primary open-angle glaucoma (POAG) or cataracts. The correlations between intraocular HODE levels and background parameters, including intraocular pressure (IOP), were analyzed to assess the possible involvement of oxidative stress in glaucoma pathology. Univariate analyses showed that linoleic acid (LA) (p = 0.034) and arachidonic acid (AA) (p = 0.0041) levels were associated negatively with age; 13-(Z,E)-HODE (p = 0.018) and 13-(E,E)-HODE (p = 0.021) were associated positively with IOP; 9-(Z,E)-HODE (p = 0.039), 13-(Z,E)-HODE (p = 0.021), totally assessed-HODE (t-HODE, p = 0.023), LA (p = 0.0080), and AA (p = 0.0051) were higher in eyes with glaucoma than cataract. No gender differences were seen. A mixed-effect regression model showed that higher 13-(Z,E)-HODE (p = 0.0040) and higher t-HODE (p = 0.040) were associated with glaucoma rather than cataracts; and higher levels of 13-(Z,E)-HODE/LA (p = 0.043), 13-(E,E)-HODE/LA (p = 0.042), 13-(Z,E)-HODE (p = 0.0054), and 13-(E,E)-HODE (p = 0.027) were associated with higher IOP. Linoleate-derived oxidation products were quantified successfully in AH samples from patients with glaucoma and cataracts. A free radical oxidation mechanism can be associated with IOP elevation, while enzymatic oxidation may be involved, specifically, in the pathogenesis of POAG.

Re-Evaluation of Rat Corneal Damage by Short-Wavelength UV Revealed Extremely Less Hazardous Property of Far-UV-C†.

Corneal damage-induced various wavelength UV (311, 254, 235, 222 and 207 nm) was evaluated in rats. For 207 and 222-UV-C, the threshold radiant exposure was between 10 000 and 15 000 mJ cm-2 at 207 nm and between 3500 and 5000 mJ cm-2 at 222 nm. Penetrate depth to the cornea indicated by cyclobutene pyrimidine dimer (CPD) localization immediately after irradiation was dependent on the wavelength. 311 and 254 nm UV penetrate to corneal endothelium, 235 nm UVC to the intermediate part of corneal stroma, 222 and 207 nm UVC only to the most outer layer of corneal epithelium. CPD observed in corneal epithelium irradiated by 222 nm UVC disappeared until 12 h after. The minimum dose to induce corneal damage of short-wavelength UV-C was considerably higher than the threshold limit value (TLV® ) promulgated by American Conference of Governmental Industrial Hygienists (ACGIH). The property that explains why UV-C radiation at 207 and 222 nm is extremely less hazardous than longer UV wavelengths is the fact that this radiation only penetrates to the outermost layer of the corneal epithelium. These cells typically peel off within 24 h during the physiological turnover cycle. Hence, short-wavelength UV-C might be less hazardous to the cornea than previously considered until today.

Effects of French maritime pine bark/bilberry fruit extracts on intraocular pressure for primary open-angle glaucoma.

We tested oral French maritime pine bark (40 mg)/bilberry fruit extract (90 mg) supplements for intraocular pressure-lowering effects in Japanese subjects with primary open-angle glaucoma. Eighteen subjects (29 eyes) were recruited with intraocular pressure of ≥15 mmHg who used one to three bottles of antiglaucoma medications. After a 2-week observation (period 1), subjects ingested a tablet/day of Sante® Glagenox for 4 weeks (period 2). The mean intraocular pressure (17.2 ± 2.3 mmHg) decreased significantly to 15.7 ± 1.9 mmHg (8.7% reduction) at week 4 (p = 0.0046). The mean morning intraocular pressure (14.1 ± 3.1 mmHg) self-measured using the iCare HOME tonometer during period 1 decreased significantly to 13.3 ± 2.9 mmHg (5.7% reduction) during period 2 (p = 0.0291). Blood redox parameters, diacron reactive oxygen metabolites, biologic antioxidant potential, and sulfhydryl tests were unchanged after 4-week supplementation. Intra-subject comparisons, compared to period 1, showed pooled, self-measured, period-2 intraocular pressures was significantly lower in nine subjects (50%), unchanged in six subjects (33%), and elevated in three subjects (17%), suggesting some non-responders. Four-week supplementation with French maritime pine bark/bilberry fruit extracts can further reduce intraocular pressure even in Japanese patients with controlled primary open-angle glaucoma. Further study should confirm the intraocular pressure-lowering effects and mechanisms of this supplement in glaucoma management. The study was registered in UMIN (ID: UMIN000033200).

Structural and Functional Change in Albino Rat Retina Induced by Various Visible Light Wavelengths.

The effects of visible light, from short to long wavelengths, on the retina were investigated functionally and histologically. The left eyes of Sprague-Dawley albino rats (6-weeks old, n = 6 for each wavelength) were exposed to seven narrow-band wavelengths (central wavelengths, 421, 441, 459, 501, 541, 581, and 615 nm) with bandwidths of 16 to 29 nm (half bandwidth, ±8-14.5 nm) using a xenon lamp source with bandpass filters at the retinal radiant exposures of 340 and 680 J/cm2. The right unexposed eyes served as controls. Seven days after exposure, flash electroretinograms (ERGs) were recorded, and the outer nuclear layer (ONL) thickness was measured. Compared to the unexposed eyes, significant reductions in the a- and b-wave ERG amplitudes were seen in eyes exposed to 460-nm or shorter wavelengths of light. The ONL thickness near the optic nerve head also tended to decrease with exposure to shorter wavelengths. The decreased ERG amplitudes and ONL thicknesses were most prominent in eyes exposed to 420-nm light at both radiant exposures. When the wavelengths were the same, the higher the amount of radiant exposure and the stronger the damage. Compared to the unexposed eyes, the a- and b-waves did not decrease significantly in eyes exposed to 500-nm or longer wavelength light. The results indicate that the retinal damage induced by visible light observed in albino rats depends on the wavelength and energy level of the exposed light.

Histologic Findings of Trabecular Meshwork and Schlemm's Canal After Microhook Ab Interno Trabeculotomy.

INTRODUCTION: Trabeculotomy (LOT) and related goniotomy surgeries are classified based on excision or incision of the trabecular meshwork (TM); however, histologic evidence of the incision/excision pattern is insufficient. CASE PRESENTATIONS: Two cases of glaucomatous eyes in which trabeculectomy specimens previously "incised" during LOT were assessed histologically. A 39-year-old man with juvenile open-angle glaucoma (case 1) and a 70-year-old man with exfoliation glaucoma (case 2) underwent trabeculectomy for insufficient intraocular pressure reduction or visual field progression after initial microhook ab interno trabeculotomy (µLOT). In case 1, Schlemm's canal (SC) opened into the anterior chamber due to extensive absence of the inner wall of SC and TM. In case 2, SC endothelium (SCE)-marker CD34 staining showed the slit-like entry site of a previous LOT, the SC lumen was sealed partially by scleral tissue, and CD34-positive and CD34-negative areas in the SC wall suggested SCE dropout and partial conversion of SC into ghost vessels. Active aqueous outflow-marker podoplanin (D2-40) staining showed intense immunolabeling in the sclera between the entry site and collector channels, indicating aqueous outflow. DISCUSSION: The µLOT cleft can appear as both incisional and excisional patterns. In addition to incremental conventional outflow with reduced TM resistance, another unconventional outflow may be a mechanism of IOP reduction after LOT procedures.

Evaluation of Redox Profiles of the Serum and Aqueous Humor in Patients with Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH.

Measurement of Force Required for Anterior Displacement of Intraocular Lenses and Its Defining Parameters.

Intraocular stability during or after cataract and glaucoma filtration surgeries and vitreous surgery with a gas/silicone oil tamponade might differ among intraocular lenses (IOLs). We used six different one-piece IOL models and measured the force that displaced the IOLs from the vitreous cavity to anterior chamber as a measure of stability against the pressure gradient between the anterior and posterior IOL surfaces. We measured IOL hardness, haptics junction area, and posterior IOL bulge to identify what determines the IOL displacement force. The KOWA YP2.2 IOL (1.231 mN) required significantly greater force than the HOYA XY1 (0.416 mN, p = 0.0004), HOYA 255 (0.409 mN, p = 0.0003), Alcon SN60WF (0.507 mN, p = 0.0010), and Nidek NS60YG (0.778 mN, p = 0.0186) IOLs; J&J ZCB00V IOL (1.029 mN) required greater force than the HOYA XY1 (p = 0.0032) and HOYA 255 (p = 0.0029) IOLs; the Nidek NS60YG IOL required greater force than the HOYA 255 (p = 0.0468) IOL. The haptics junction area was correlated positively with the IOL displacement force (r = 0.8536, p = 0.0306); the correlations of the other parameters were non-significant. After adjusting for any confounding effects, the haptics junction area was correlated significantly with the IOL displacement force (p = 0.0394); the IOL hardness (p = 0.0573) and posterior IOL bulge (p = 0.0938) were not. The forces that displace IOLs anteriorly differed among one-piece soft-acrylic IOLs, and the optics/haptics junction area was the major force determinant.

Long-term Effects of 222-nm ultraviolet radiation C Sterilizing Lamps on Mice Susceptible to Ultraviolet Radiation.

Germicidal lamps that emit primarily 254 nm ultraviolet radiation (UV) are routinely utilized for surface sterilization but cannot be used for human skin because they cause genotoxicity. As an alternative, 222-nm UVC has been reported to exert sterilizing ability comparable to that of 254-nm UVC without producing cyclobutane pyrimidine dimers (CPDs), the major DNA lesions caused by UV. However, there has been no clear evidence for safety in chronic exposure to skin, particularly with respect to carcinogenesis. We therefore investigated the long-term effects of 222-nm UVC on skin using a highly photocarcinogenic phenotype mice that lack xeroderma pigmentosum complementation group A (Xpa-) gene, which is involved in repairing of CPDs. CPDs formation was recognized only uppermost layer of epidermis even with high dose of 222-nm UVC exposure. No tumors were observed in Xpa-knockout mice and wild-type mice by repetitive irradiation with 222-nm UVC, using a protocol which had shown to produce tumor in Xpa-knockout mice irradiated with broad-band UVB. Furthermore, erythema and ear swelling were not observed in both genotype mice following 222-nm UVC exposure. Our data suggest that 222-nm UVC lamps can be safely used for sterilizing human skin as far as the perspective of skin cancer development.

Association between Systemic Antioxidant Capacity and Retinal Vessel Diameters in Patients with Primary-Open Angle Glaucoma.

The retinal vessel narrowing may be implicated in the pathogenesis of glaucoma; however, the association between systemic oxidative stress and retinal vessel diameter remains largely unknown. We examined the relationship between serum oxidative stress markers and retinal vessel diameters in eyes with primary open-angle glaucoma (POAG) and cataract, using central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). We included 66 eyes of 66 patients with POAG (37 men, 29 women; 65.4 ± 11.7 years) and 20 eyes of 20 patients with cataract (7 men, 13 women; 69.4 ± 9.0 years) as the controls. The CRAE (p < 0.0001), CRVE (p < 0.0001), and serum biological antioxidant potential (BAP) (p = 0.0419) were significantly lower in the POAG group compared to the controls. The BAP showed significant correlation both with CRAE (ρ = 0.2148, p = 0.0471) and systolic blood pressure (ρ = -0.2431, p = 0.0241), while neither Diacron reactive oxygen metabolites nor sulfhydryl test correlated with them. The multivariate analyses indicated that age, best corrected visual acuity, and BAP were independent factors for CRAE or CRVE. The present study suggested that lower systemic antioxidant capacity was significantly associated with the intraocular pressure-independent vascular narrowing in POAG patients. This study provided a novel insight into the pathophysiology of glaucoma and highlighted the clinical impact on systemic antioxidant treatment for patients with glaucoma.

Involvement of free radical-mediated oxidation in the pathogenesis of pseudoexfoliation syndrome detected based on specific hydroxylinoleate isomers.

We reported previously that enzymatic and singlet oxygen-mediated fatty acid oxidation may be major oxidation pathways in subjects with primary open angle glaucoma, based on measurement of serum levels of hydroxylinoleate (HODE) and hydroxyarachidonate (HETE) isomers after reduction and saponification. In this study, we measured serum levels of HODE and HETE isomers to investigate the pathogenesis of exfoliation syndrome (EX). In total, 311 Japanese subjects comprising EX patients (n = 192) and non-glaucomatous control subjects (n = 119) were included in this study. Patients with EX (n = 192) were divided into EX with glaucoma (EXG) and EX without glaucoma (EXS) groups (n = 128 and n = 64, respectively) depending on the intraocular pressure. Total HODE (/linoleic acid) serum levels were significantly (p = 0.0426) higher in the EX group (202.7 ± 153.2 µmol/mol) than in the controls (167.1 ± 105.3 µmol/mol). Among the HODE isomers, the levels of 9-(E,E)-HODEs (p < 0.0001) and 13-(E,E)-HODEs (p < 0.0001), both free radical-mediated oxidation products, were higher in the EX and EXG groups than in the controls, whereas no significant difference was observed between EXS and controls. After adjusting for differences in demographic parameters, multivariate analyses confirmed the association between 9- and 13-(E,E)-HODEs and EX. This is the first report of a dramatic increase in free radical-mediated oxidation products related to the pathogenesis of EX, and our findings suggest that free radical-mediated oxidation can be one of the causes of deterioration in EX.

Suppression of Light-Induced Retinal Degeneration by Quercetin via the AP-1 Pathway in Rats.

We examined the cytoprotective effect of quercetin via activator protein (AP-1) and the heat shock protein 70 (Hsp70) pathway against light-induced retinal degeneration in rats. Quercetin was administered intraperitoneally to Sprague-Dawley rats for seven days before light exposure to intense white fluorescent light (3000 lux) for 24 h. Light-induced retinal damage was determined by the number of rows of photoreceptor cell nuclei, the microstructures of the rod outer segments and retinal pigment epithelium, and terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine-5'-triphosphate (dUTP) nick end labeling. To elucidate the cytoprotective mechanism of quercetin, expression levels were measured in the rat retinas of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative stress; Hsp70; and transcription factor AP-1 transcription activity. Pretreatment with quercetin inhibited light-induced photoreceptor cellular apoptosis and subsequent retinal degeneration in rats. 8-OHdG and Hsp70 protein expressions were up-regulated markedly by light exposure and suppressed by quercetin pretreatment. The results of an electrophoretic mobility shift assay showed that AP-1-binding activity was activated by light exposure, and binding of c-Fos and c-Jun, but not JunB, mediated the binding activity. Intraperitoneal administration of quercetin decreases photooxidative damage in the retina and mediates cytoprotection against light-induced photoreceptor cell degeneration in rats. Suppression of the heterodimeric combination of c-Jun and c-Fos proteins at the AP-1 binding site is highly involved in quercetin-mediated cytoprotection.