UVR-B-induced NKR-1 Expression in Ocular Tissues is blocked by Substance P Receptor Antagonist Fosaprepitant in the Exposed as well as Unexposed Partner Eye.

Purpose: To investigate the effect of NKR-1 antagonists in an established UVR-B-induced cataract mouse model. Furthermore, to examine the expression of pro-inflammatory cytokines/chemokines in mouse eyes following unilateral UVR-B exposure.Methods: Mice received intraperitoneally injections of Fosaprepitant and Spantide I, before and after unilateral exposure to UVR-B. After day 3 and 7 post-exposure, ocular tissues were extracted for the detection of NKR-1 protein level by ELISA.Results: Pretreatment with Fosaprepitant decreases NKR-1 expression in exposed ocular tissues as well as in the unexposed lens epithelium compared to the saline group. Spantide I treatment showed a tendency of NKR-1 overexpression in ocular tissues.Conclusion: The clinically approved NKR-1 receptor antagonist Fosaprepitant decreases NKR-1 protein expression effectively not only in the exposed but also in the unexposed partner eye in a UVR-B irradiation mouse model. No effect was seen on the protein concentration of pro-inflammatory cytokines/chemokines in either eye.

Ultraviolet Radiation Exposure of One Eye Stimulates Sympathizing Expression of Neurokinin-1 Receptor but Not Monocyte Chemoattractant Protein-1 in the Partner Eye.

PURPOSE: To investigate the influence of unilateral ultraviolet radiation (UVR) exposure on the unexposed, partner eye in vivo. To characterize the immunological cross-talk between the eyes and verify a sympathizing reaction of the partner eye via a neurokinin-dependent signaling pathway of substance P and its neurokinin-1 receptor (NKR-1) and/or monocyte chemoattractant protein-1 (MCP-1). METHODS: C57BL/6 mice were unilaterally exposed in vivo to UVR-B to a 5-fold cataract threshold equivalent dose of 14.5 kJ/m2 with a UV irradiation Bio-Spectra system. The unexposed contralateral eye was completely shielded during irradiation. After 3 and 7 days post exposure, eyes were stained with fluorescence-coupled antibody for substance P NKR-1. The same was performed in control animals receiving only anesthesia but no UVR-B exposure. NKR-1 and MCP-1 levels in ocular tissue lysates were quantified by enzyme-linked immunosorbent assay. RESULTS: UVR-B induces NKR-1 upregulation after 3 and 7 days in the exposed and in the unexposed, contralateral mouse eye. NKR-1 protein level was upregulated in the exposed and contralateral iris/ciliary body complex, choroidea and in the contralateral retina as well as in the exposed cornea. MCP-1 levels were elevated in the exposed cornea, iris/ciliary body complex, and aqueous humor but not in contralateral ocular tissues. CONCLUSIONS: UVR-B exposure triggers NKR-1 upregulation not only in the exposed but also in the unexposed, partner eye in various ocular tissues. Following UVR-B exposure, MCP-1 protein levels are upregulated in the exposed eye, but the contralateral side remains unaffected.

Ultraviolet radiation exposure triggers neurokinin-1 receptor upregulation in ocular tissues in vivo.

The purpose of this study was to investigate the neurokinin receptor-1 (NKR-1) protein expression in ocular tissues before and after supra-cataract threshold ultraviolet radiation (UVR-B peak at 312 nm) exposure in vivo in a mouse model. Six-week-old C57Bl/6 mice were unilaterally exposed to a single (2.9 kJ/m2) and an above 3-fold UVR-B cataract threshold dose (9.4 kJ/m2) of UVR. UVR-exposure (λpeak = 312 nm) was performed in mydriasis using a Bio-Spectra exposure system. After latency periods of 3 and 7 days, eyes were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned and stained with fluorescence coupled antibody for NKR-1 and DAPI for cell nuclei staining. Control animals received only anesthesia but no UVR-exposure. Cataract development was documented with a Leica dark-field microscope and quantified as integrated optical density (IOD). NKR-1 is ubiquitously present in ocular tissues. An above 3-fold cataract threshold dose of UV-radiation induced NKR-1 upregulation after days 3 and 7 in the epithelium and endothelium of the cornea, the endothelial cells of the iris vessels, the pigmented epithelium/stroma of the ciliary body, the lens epithelium, pronounced in the nuclear bow region and the inner plexiform layer of the retina. A significant upregulation of NKR-1 could not be provoked with a single cataract threshold dose (2.9 kJ/m2 UVR-B) ultraviolet irradiation. All exposed eyes developed anterior subcapsular cataracts. Neurokinin-1 receptor is present ubiquitously in ocular tissues including the lens epithelium and the nuclear bow region of the lens. UV-radiation exposure to an above 3-fold UVR-B cataract threshold dose triggers NKR-1 upregulation in the eye in vivo. The involvement of inflammation in ultraviolet radiation induced cataract and the role of neuroinflammatory peptides such as substance P and its receptor, NKR-1, might have been underestimated to date.

Incidence of cystoid macular edema following secondary posterior chamber intraocular lens implantation.

PURPOSE: To investigate the incidence and risk factors for the occurrence of cystoid macular edema (CME) after secondary posterior chamber intraocular lens (PC IOL) fixation. SETTING: Eye Clinic Herzog Carl Theodor, Munich, Germany. DESIGN: Retrospective case series. METHODS: Eyes with secondary PC IOL implantation were included. Eyes in Group 1 were treated because of preexisting aphakia; eyes in Group 2 had reimplantation or refixation of a failed primary PC IOL (Group 2). Patients were followed for at least 12 months with measurement of corrected distance visual acuity (CDVA) and central retinal thickness with optical coherence tomography (OCT). Risk factors for CME occurrence were evaluated with standard statistical procedures. Cutoff points of sensitivity and specificity were calculated for the prediction of CME with the receiver operating characteristic (ROC) method. RESULTS: Forty-two eyes of 40 patients (16 men, 24 women; mean age 75.4 years ± 13.7 [SD]) were included. There were 28 eyes in Group 1 and 14 eyes in Group 2. Seven eyes (16.7%) developed CME with significant impairment of CDVA and an increase in central retinal thickness on OCT. Five eyes in Group 1 and 2 eyes in Group 2 were affected, without a significant difference between groups. The CDVA after surgery had a significant influence, and there was a trend toward patient age as a risk factor. The ROC analysis yielded 83.9 years of age and a CDVA of 0.35 logMAR, respectively, as meaningful cutoff points. CONCLUSIONS: Secondary PC IOL fixation was performed with good results despite the inherent CME risk from the procedure. Advanced age and poor CDVA after surgery might predict CME occurrence. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Bilateral Simultaneous Retinal Detachment in Pseudophakia.

Cataract surgery is the most frequent surgical intervention, with approximately 700,000 operations per year in Germany alone. One of the most serious complications is retinal detachment, with a reported incidence rate of pseudophakic retinal detachment of 0.75-1.65%. We report the case of a patient who suffered from a simultaneous bilateral pseudophakic retinal detachment. Interestingly, the bilateral detachments in the left and the right eye started with only some hours' delay. He had no acute trigger for the retinal detachment and no risk factors besides the cataract surgery performed on both eyes some weeks earlier. Simultaneous bilateral retinal detachments will be more common, due to increasing numbers of cataract surgeries and the demographic development. We conclude that funduscopy should be regularly performed in mydriasis to avoid sight-threatening simultaneous bilateral retinal detachments.

Effect of Viscous Agents on Corneal Density in Dry Eye Disease.

PURPOSE: To investigate the effect of the viscous agents, hydroxypropyl methylcellulose (HPMC), carbomer, povidone, and a combination of HPMC and povidone on corneal density in patients with dry eye disease. METHODS: In total, 98 eyes of 49 patients suffering from dry eye and 65 eyes of 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and corneal density was analyzed in 5 anatomical layers (epithelium, bowman membrane, stroma, descemet's membrane, and endothelium). Corneal density was evaluated for the active ingredients HPMC, carbomer, povidone, and a combination of HPMC and povidone as the viscous agents contained in the artificial tear formulations used by the dry eye patients. Data were compared to the age-matched healthy control group without medication. RESULTS: Corneal density in dry eye patients was reduced in all 5 anatomical layers compared to controls. Corneal density was highest and very close to control in patients treated with HPMC containing ocular lubricants. Patients treated with lubricants, including carbomer as the viscous agent displayed a significant reduction of corneal density in layers 1 and 2 compared to control. CONCLUSION: HPMC containing ocular lubricants can help to maintain physiological corneal density and may be beneficial in the treatment of dry eye disease.

Two-year outcome of repeat trabeculectomy with mitomycin C in primary open-angle and PEX glaucoma.

PURPOSE: To evaluate the effectiveness of repeat trabeculectomy with risk factor-adjusted mitomycin C (MMC) application in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) over 2 years. METHODS: A total of 58 patients (43 with POAG, 15 with PEXG) who had undergone repeat trabeculectomy with MMC were included in this retrospective study. Exposure time of MMC 0.3 mg/mL was adjusted according to a standardized protocol. Main outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP) reduction, surgical success rate (criteria were defined as A: IOP ≤21 mm Hg and a reduction of IOP ≥20%; B: IOP ≤18 mm Hg and a reduction of IOP of ≥30%; C: IOP ≤15 mm Hg and a reduction of IOP of ≥40% from baseline), and number of medications at baseline, 3 months, and 2 years postoperatively. RESULTS: The BCVA remained stable for 2 years after surgery (0.47 ± 0.47 at baseline, 0.49 ± 0.64 logMAR units after 2 years, respectively). Mean IOP decreased from 22.2 ± 7.0 mm Hg at baseline to 12.7 ± 3.1 mm Hg at 3 months and 12.9 ± 4.3 mm Hg 2 years after surgery. The qualified success rate for criterion A was 75.4%, for criterion B 66.6%, and for criterion C45.6%. Complete success rates were 42.9%, 37.5%, and 32.1%, respectively. Two years after repeat trabeculectomy, the mean IOP was reduced by 38.8%, and the number of medications was reduced significantly. CONCLUSIONS: Repeat trabeculectomy with MMC is successful at lowering IOP in POAG and PEXG and permits a significant and safe reduction of antiglaucomatous medication for at least 2 years after surgery.

Delayed macular hole closure.

PURPOSE: The presented case raises questions regarding the favorable scheduling of planned postoperative care and the ideal observation interval to decide for reoperations in macular hole surgery. Furthermore a discussion about the use of short- and long-acting gas tamponades in macular hole surgery is encouraged. METHODS: We present an interventional case report and a short review of the pertinent literature. RESULTS: We report a case of spontaneous delayed macular hole closure after vitreoretinal surgery had been performed initially without the expected success. A 73-year-old male Caucasian patient presented at our clinic with a stage 2 macular hole in his left eye. He underwent 23-gauge pars plana vitrectomy and internal limiting membrane peeling with a 20% C2F6-gas tamponade. Sixteen days after the procedure, an OCT scan revealed a persistent stage 2 macular hole, and the patient was scheduled for reoperation. Surprisingly, at the date of planned surgery, which was another 11 days later, the macular hole had resolved spontaneously without any further intervention. CONCLUSIONS: So far no common opinion exists regarding the use of short- or long-acting gas in macular hole surgery. Our case of delayed macular hole closure after complete resorption of the gas tamponade raises questions about the need and duration of strict prone positioning after surgery. Furthermore short-acting gas might be as efficient as long-acting gas. We suggest to wait with a second intervention at least 4 weeks after the initial surgery, since a delayed macular hole closure is possible.

Pharmacokinetics for topically applied caffeine in the rat.

Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.

Ultrastructure of UVR-B-induced cataract and repair visualized with electron microscopy.

PURPOSE: The aim of the study is to investigate and visualize the ultrastructure of cataract morphology and repair, after in vivo exposure to double threshold dose UVR-B in the C57BL/6 mouse lens. METHODS: Twenty-six-week-old C57BL/6 mice received in vivo double threshold dose (6.4 kJ/m2) UVR-B for 15 min. The radiation output of the UVR-source had λMAX at 302.6 nm. After a latency period of 1, 2, 4 and 8 days following UVR-B exposure, the induced cataract was visualized with electron microscopy techniques. Induced, cataract was quantified as forward lens light scattering. Damage to the lens epithelium and the anterior cortex was investigated with light microscopy in toluidine blue-stained semi-thin sections, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and dark field illumination photography. RESULTS: UVR-B-exposed lenses developed anterior subcapsular and/or cortical and nuclear cataract after 1 day. Lens light scattering peaked 2 days after exposure. Lens epithelial cell damage was seen in TEM as apoptotic cells, apoptotic bodies, nuclear chromatin condensation, and swollen and disrupted anterior cortex fibres throughout the sections of the whole anterior lens surface. These morphologic changes were also visualized with SEM. Within 8 days, anterior subcapsular cataract was repaired towards the anterior sutures. CONCLUSION: UVR-B exposure of double cataract threshold dose induces a subtotal loss of epithelial cells across the whole anterior surface of the lens. This damage to the epithelium is repaired by epithelial cell movement from the equator towards the lens sutures, thus in retrograde direction to regular epithelial cell differentiation.

Evolution of TUNEL-labeling in the rat lens after in vivo exposure to just above threshold dose UVB.

PURPOSE/AIM: To quantitatively analyse the evolution of TUNEL-labeling, after in vivo exposure to UVB. METHODS: Altogether, 16 Sprague Dawley rats were unilaterally exposed in vivo for 15 min to close to threshold dose, 5 kJ/m(2), of ultraviolet radiation in the 300 nm wavelength region. Animals were sacrificed in groups of 4 at 1, 5, 24 and 120 h after exposure. For each animal, both eye globes were removed and frozen. The frozen eye was cryo-sectioned in 10 µm thick midsagittal sections. From each globe, three midsagittal sections with at least five sections interval in between were mounted on a microscope slide. Sections were TUNEL-labeled and counter stained with DAPI. For quantification of apoptosis, a fluorescence microscope was used. In sections with a continuous epithelial cell surface, the number of lens epithelial cell nuclei and the number of TUNEL-positive epithelial cell nuclei was counted. The total number of TUNEL-positive epithelial cell nuclei for all three sections of one lens in relation to the total number of epithelial cell nuclei for all three sections of the same lens was compared between exposed and contralateral not exposed lens for each animal. RESULTS: The relative difference of the fraction of TUNEL-positive nuclei between exposed and contralateral not exposed lens increased gradually, peaked in the time interval 5-120 h after exposure, and then declined. CONCLUSIONS: Close to threshold dose of UVB induces TUNEL-labeling that peaks in the time window 5-120 h after exposure to UVB.

Secondary glaucoma after intravitreal dexamethasone 0.7 mg implant in patients with retinal vein occlusion: a one-year follow-up.

PURPOSE: To investigate the rate of secondary glaucoma after intravitreal dexamethasone 0.7 mg (Ozurdex(®)) implantation over a clinical treatment period of 1 year. METHODS: A prospective study of a series of 16 patients (9 males, 7 females; mean age 76 years) suffering from central- or branch retinal vein occlusion treated with dexamethasone 0.7 mg were followed up for 12 months. Main outcome measures were intraocular pressure (IOP) determined with Goldmann applanation tonometry (GAT) and Pascal dynamic contour tonometry (DCT), as well as best-corrected visual acuity (BCVA) and central retinal thickness measured with optical coherence tomography (OCT). RESULTS: BCVA (logMAR) improved in treated patients from mean 0.81 at baseline to a peak of 0.47 after 2 months but declined irrespective of reinjections to 0.87 at 12 months. Central retinal thickness measured with OCT initially decreased but increased again with recurring macular edema. 69% of patients treated with dexamethasone 0.7 mg had an IOP increase of at least 5 mmHg. In total, 50% of patients had an increase of ≥10 mmHg during the studied period. The IOP increase in treated eyes was significant 1, 2, 3, and 8 months after dexamethasone 0.7 mg implantation. CONCLUSION: Secondary glaucoma after intravitreal injection of dexamethasone 0.7 mg might be underestimated in the GENEVA studies. The clinical safety profile reported here calls for thorough identification of suitable patients and frequent IOP control if dexamethasone 0.7 mg (Ozurdex) is applied as a long-term treatment.

Bilateral cataract induced by unilateral UVR-B exposure -- evidence for an inflammatory response.

PURPOSE: To investigate whether unilateral in vivo UVR-B exposure of one eye affects the fellow eye in a co-cataractogenic, sympathetic reaction and to determine whether an inflammatory response could be involved in the pathogenesis. METHODS: C57BL/6 mice were unilaterally exposed in vivo to UVR-B for 15 min. In the group of 24 animals each received 0×/2×/3×/or 4× cataract threshold equivalent dose. Following 48-hr UVR-B exposure, cataract morphology was documented in dark-field illumination photography, and light scattering was quantified, in both lenses in vitro. Serum levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were analysed with ELISA. Immunohistochemistry was performed for inflammatory infiltration in exposed and contralateral eyes. RESULTS: UVR-B exposure induced cataract in all exposed lenses. There was additionally a significant UVR dose-dependent increase in light scattering in the lenses of the non-exposed fellow eye. Inflammatory infiltration was detected immunohistochemically in the anterior segment of both eyes. IL-1ß serum concentration increased with increasing UVR-B exposure dose. There was a similar trend for serum IL-6 but not for TNF-α. CONCLUSION: Unilateral UVR-B exposure to one eye is associated with intraocular inflammation and an increase in lens light scattering also in the unexposed, fellow eye. A resulting systemic inflammatory response might be mediated by IL-1ß and possibly IL-6. The finding that an inflammatory response may play a role in UVR-B-induced cataract development might initiate new strategies in the prevention of the disease.

Cystoid Macular Edema after Complicated Cataract Surgery Resolved by an Intravitreal Dexamethasone 0.7-mg Implant.

PURPOSE: To report the effective treatment of cystoid macular edema (CME) following complicated cataract surgery (resulting in Irvine-Gass syndrome) with a dexamethasone 0.7-mg (Ozurdex(®)) intravitreal implant. METHODS: An interventional case report with optical coherence tomography (OCT) scans. RESULTS: An 83-year-old Caucasian woman was suffering from CME following complicated cataract surgery on her left eye. She had undergone 3 intravitreal injections of dexamethasone 0.4 mg in the 3 months following the surgery without any improvement of visual function. Seven months after the cataract surgery, she received a single intravitreal injection of dexamethasone 0.7 mg (Ozurdex). Four weeks following the injection, her best-corrected visual acuity improved from 0.3 to 0.8. CME resolved with a reduction of central retinal thickness from 393 µm pre-Ozurdex injection to 212 µm post-Ozurdex injection, as measured by OCT scan. CONCLUSION: Dexamethasone 0.7 mg (Ozurdex) has proven to be an effective treatment option in retinal vein occlusion and non-infectious uveitis. It can also be considered as off-label treatment in Irvine-Gass syndrome.

Fast Resolution of Recurrent Pronounced Macular Edema following Intravitreal Injection of Dexamethasone 0.7 mg.

PURPOSE: To report the fast resolution of recurrent pronounced macular edema due to central retinal vein occlusion (CRVO) within 72 h following intravitreal injection of dexamethasone 0.7 mg (Ozurdex®). METHODS: An interventional case report with optical coherence tomography scans and fluorescein angiographic pictures. RESULTS: A 69-year-old Caucasian man underwent intravitreal injection of dexamethasone 0.7 mg due to incomplete CRVO. He had previously undergone 6 intravitreal injections of bevacizumab 1.25 mg (Avastin®) and a C-grid laser photocoagulation over an interval of 16 months. After repeated recurrences of macular edema, the injection of dexamethasone reduced the macular edema from 570 µm preoperatively to 246 µm postoperatively within 72 h following the injection. Best-corrected visual acuity improved from 0.1 to 0.6 within the same interval. CONCLUSION: Dexamethasone can lead to a very fast reduction of macular edema in patients with vision loss due to CRVO and may facilitate an immediate visual rehabilitation. Retinal anatomy and visual acuity may be restored even in long-standing, recurrent cases.

Absence of glutaredoxin1 increases lens susceptibility to oxidative stress induced by UVR-B.

We investigated if the absence of glutaredoxin1, a critical protein thiol repair enzyme, increases lens susceptibility to oxidative stress caused by in vivo exposure to ultraviolet radiation type B (UVR-B). Glrx(-/-) mice and Glrx(+/+) mice were unilaterally exposed in vivo to UVR-B for 15 min. Groups of 12 animals each received 4.3, 8.7, and 14.5 kJ/m(2) respectively. 48 h post UVR-B exposure, the induced cataract was quantified as forward lens light scattering. Cataract morphology was documented with darkfield illumination photography. Glutathione (GSH/GSSG) content was analyzed in Glrx(-/-) and Glrx(+/+) lenses. UVR-B exposure induced anterior sub-capsular cataract (ASC) in Glrx(-/-) and Glrx(+/+) mice. In Glrx(-/-) lenses the opacities extended further towards the lens equator than in wild type animals (Glrx(+/+)). Lens light scattering in Glrx(-/-) mice was increased in all dose groups compared to lenses with normal glutaredoxin1 function. The difference was more pronounced with increasing exposure dose. Lens sensitivity for UVR-B induced damage was significantly higher in Glrx(-/-) lenses compared to Glrx(+/+) lenses. The Glrx gene provides a 44% increase of protection against close to threshold UVR-B induced oxidative stress compared to the absence of the Glrx gene. In conclusion, the absence of glutaredoxin1 increases lens susceptibility to UVR-B induced oxidative stress in the mouse.

Dose dependent cataractogenesis and Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in C57BL/6J mice.

The purpose of the present study was to investigate the in vivo dose response function for UVR 300 nm-induced cataract in the C57BL/6J mouse lens and to establish a cataract threshold estimate expressed as Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in the C57BL/6J mouse lens. Knowledge of the MTD(2.3:16) in the C57BL/6J mouse will permit quantitative in vivo comparison of UVR-B threshold sensitivity of knockout mice, e.g. animals deficient in key antioxidative enzymes or mice suffering from genetically predetermined eye disease, to wild type animals. Eighty C57BL/6J mice were divided into four dose groups. The animals were exposed unilaterally to 0, 2, 4, or 8 kJ/m(2) UVR 300 nm for 15 min (n=20). The radiation output of the UVR-source had lambda(max) at 302.6 nm with 5 nm full width at half maximum. Two days after exposure cataract was quantified as forward lens light scattering intensity in the exposed and the contralateral non-exposed lens. Morphological lens changes were documented using grid and dark field illumination photography. MTD(2.3:16) was estimated from the forward light scattering measurements. Two days after exposure mainly anterior subcapsular but also cortical and nuclear cataract developed in lenses that had received 2, 4, and 8 kJ/m(2) UVR 300 nm. Forward light scattering intensity increased with increasing UVR 300 nm dose. MTD(2.3:16) for the mouse lens was estimated to 2.9 kJ/m(2) UVR 300 nm. Lens light scattering intensity in the C57BL/6J mouse lens increases with UVR 300 nm in vivo dose in the range 0-8 kJ/m(2). The MTD(2.3:16) of 2.9 kJ/m(2) in the C57BL/6J mouse lens determined here, is essential to quantify and compare in vivo the impact of genetic modulation on lens susceptibility to oxidative stress and plan dose-ranges in future investigations of UVR 300 nm-induced cataract pathogenesis.

Light scattering in the C57BL/6 mouse lens.

PURPOSE: To characterize inherent light scattering in the C57BL/6 mouse lens. METHODS: Lenses from 20 6-week-old female C57BL/6 mice were extracted from freshly enucleated globes and microsurgically cleaned of remnants of the ciliary body. Lens light scattering was measured quantitatively with a light dissemination meter (LDM). Morphological properties of the mouse lenses were documented using grid- and dark-field illumination photography. Analysis of variance was performed to establish variance for animals, variance between left and right eyes and variance for measurements. RESULTS: Average inherent light scattering in the C57BL/6 mouse lens is 0.16 +/- 0.02 tEDC (transformed equivalent diazepam concentration). The mean size of a mouse lens at 6 weeks is 1.9 mm in diameter. Two lenses featured pre-existing cortical lens opacities. Variance for animals was assessed to be 7.9 10(- 4) tEDC(2), variance for measurements was 1.6 10(- 4) tEDC(2), and variance between left and right eyes was 8.8 10(- 4) tEDC(2). The tolerance limit for non-pathological light scattering was determined to 0.26 tEDC. No significant difference in light scattering between left and right mouse lenses was found. The minimum number of C57BL/6 mice required for detection of a 10% experimentally induced change in light scattering intensity was estimated to be 50 for independent group experiments and 25 for paired design experiments. CONCLUSIONS: The C57BL/6 mouse is a suitable animal in which to conduct experiments on light scattering or cataractogenesis with high precision at reasonable sample sizes. Before including C57BL/6 mice into a study on cataractogenesis, pre-existing lens opacities such as congenital cataract must be excluded.

UVR-B induced cataract development in C57 mice.

The evolution of the morphological appearance and intensity of light scattering in C57 mice lenses after exposure to ultraviolet radiation type B (UVR-B) was investigated. A total of 80, 6-week-old female C57BL/6 mice were divided into four groups (n=20). One eye in each animal was exposed in vivo to UVR-B in the 300 nm wavelength region (UVR-B-300 nm) to a dose of 5 kJm(-2) for 15 min. The radiation output had lambda(max) at 302 nm with 5 nm [FWHM]. The animals were consecutively sacrificed at 1, 2, 4 and 8 days after the exposure. Macroscopic lens changes were documented using grid- and dark field illumination photography. Light scattering in the exposed and contralateral not exposed lens was measured quantitatively. Morphological lens changes were documented using grid- and dark field illumination photography. In vivo exposure to UVR-B-300 nm induced subcapsular cataract in all exposed lenses and occasionally cortical and nuclear cataract at all investigated time points. Exposed lenses scattered light significantly higher on all investigated days compared to contralateral non-exposed lenses. A transient increase of light scattering peaking at day 2 in exposed as well as in contralateral not exposed lenses was identified. Light scattering of the lenses varies with latency time after exposure. A dose of 5 kJm(-2) UVR-B-300 nm induces light scattering in C57 mice lenses. The increase has a transient peak at 2 days after exposure. The variation of light scattering among days 1, 2, 4, and 8 indicates a dynamic change of scattering characteristics in the mouse lens following unilateral in vivo exposure to 5 kJm(-2) UVR-B-300 nm.

Polyoxoanion Coordination Chemistry: Synthesis and Characterization of the Heterometallic, Hexanuclear Clusters [{Zn(bipy)(2)}(2)V(4)O(12)], [{Zn(phen)(2)}(2)V(4)O(12)].H(2)O, and [{Ni(bipy)(2)}(2)Mo(4)O(14)].

The hydrothermal reactions of vanadium oxide and molybdenum oxide starting materials with divalent first-row transition metal cations in the presence of nitrogen donor chelating ligands yield the heterometallic hexanuclear clusters [{Zn(bipy)(2)}(2)V(4)O(12)] (2), [{Zn(phen)(2)}(2)V(4)O(12)].H(2)O (3.H(2)O), and [{Ni(bipy)(2)}(2)Mo(4)O(14)] (4). A similar reaction in the presence of excess 2,2'-bipyridine yields [Zn(bipy)(3)](2)[V(4)O(12)].11H(2)O (1.11H(2)O), a species with an isolated {V(4)O(12)}(4)(-) cluster. The structure of 2 consists of a {V(4)O(12)}(4)(-) ring covalently attached to each of two {Zn(bipy)(2)}(2+) moieties through the terminal oxo groups of alternate vanadium sites. In contrast, the structure of 3 exhibits a {V(4)O(12)}(4)(-) ring linked through oxo groups of adjacent vanadium sites to two {Zn(phen)(2)}(2+) moieties. The structure of 4 is constructed from two {Mo(2)O(7)}(2)(-) units linked through two {Ni(bipy)(2)}(2+) groups to form a cyclic 12-membered {Mo(4)Ni(2)O(6)} core. Crystal data: [Zn(bipy)(3)](2)[V(4)O(12)].11H(2)O (1.11H(2)O), a = 21.910(4) Å, b = 14.044(2) Å, c = 23.815(4) Å, beta = 106.15(1) degrees, monoclinic, C2/c, Z = 4; [{Zn(bipy)(2)}(2)V(4)O(12)] (2), a = 12.017(2) Å, c = 15.120(2) Å, tetragonal P4(2)/n, Z = 2. [{Zn(o-phen)(2)}(2)V(4)O(12)].H(2)O (3.H(2)O), a = 18.182(2) Å, b = 11.3668(9) Å, c = 23.455(2) Å, beta = 97.815(7) degrees, monoclinic P2(1)/c, Z = 4; [{Ni(bipy)(2){(2)Mo(4)O(14)] (4), a = 12.323(2) Å, c = 14.897(4) Å, tetragonal P4(2)2(1)2, Z = 2.