Osteochondrosis of the humeral capitellum can be successfully treated conservatively if treatment is begun in an early stage of the disease.

No abstract

Retinitis pigmentosa (RP) is a collection of diseases in which rod photoreceptors die from a variety of mutations. After rods die, the level of tissue oxygen in the outer retina becomes elevated and there is progressive oxidative damage to cones that ultimately triggers apoptosis. In this study, we investigated the hypothesis that NADPH oxidase (Nox) and/or xanthine oxidase serve as critical intermediaries between increased tissue oxygen and the generation of excessive reactive oxygen species that cause oxidative damage to cones. Apocynin, a blocker of Nox, but not allopurinol, a blocker of xanthine oxidase, markedly reduced the superoxide radicals visualized by hydroethidine in the outer retina in the retinal degeneration‐1 (rd1+/+) model of RP. Compared to rd1+/+ mice treated with vehicle, those treated with apocynin, but not those treated with allopurinol, had significantly less oxidative damage in the retina measured by ELISA for carbonyl adducts. Apocynin‐treated, but not allopurinol‐treated, rd1+/+ mice had preservation of cone cell density, increased mRNA levels for m‐ and s‐cone opsin, and increased mean photopic b‐wave amplitude. In Q344ter mice, a model of dominant RP in which mutant rhodopsin is expressed, apocynin treatment preserved photopic electroretinogram b‐wave amplitude compared to vehicle‐treated controls. These data indicate that Nox, but not xanthine oxidase, plays a critical role in generation of the oxidative stress that leads to cone cell death in RP and inhibition of Nox provides a new treatment strategy.

Digoxin and other cardiac glycosides inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity in cultured cells and suppress tumor xenograft growth. We tested the hypothesis that digoxin reduces HIF-1 levels in ischemic tissue in vivo and suppresses neovascularization. Well-established murine models of ocular neovascularization were used to test our hypothesis. In mice with ischemic retinopathy, intraocular or intraperitoneal injection of digoxin markedly reduced retinal levels of HIF-1alpha protein and mRNAs encoding multiple hypoxia-regulated proangiogenic proteins and their receptors. Daily intraperitoneal injection of 2 mg/kg starting at postnatal day (P) 12 or a single intravitreous injection of 100 ng of digoxin at P12 reduced retinal neovascularization by >70% at P17. Digoxin also reduced the number of CXCR4(+) cells and F4/80(+) macrophages in ischemic retina and significantly reduced choroidal neovascularization at Bruch's membrane rupture sites. Digoxin suppresses retinal and choroidal neovascularization by reducing HIF-1alpha levels, which blocks several proangiogenic pathways. Since digoxin suppresses multiple pathways in addition to VEGF signaling, it may provide advantages over specific VEGF antagonists for treatment of patients with retinal and choroidal diseases complicated by neovascularization and/or excessive vascular permeability. It may also be useful for treatment of neovascular diseases in other tissues.

Two constituents of bile, bilirubin and tauroursodeoxycholic acid (TUDCA), have antioxidant activity. However, bilirubin can also cause damage to some neurons and glial cells, particularly immature neurons. In this study, we tested the effects of bilirubin and TUDCA in two models in which oxidative stress contributes to photoreceptor cell death, prolonged light exposure and rd10+/+ mice. In albino BALB/c mice, intraperitoneal (IP) injection of 5 mg/kg of bilirubin or 500 mg/kg of TUDCA prior to exposure to 5,000 lux of white light for 8 hours significantly reduced loss of rod and cone function assessed by electroretinograms (ERGs). Both treatments also reduced light-induced accumulation of superoxide radicals in the outer retina, rod cell death assessed by outer nuclear layer (ONL) thickness, and disruption of cone inner and outer segments. In rd10+/+ mice, IP injections of 5 or 50 mg/kg of bilirubin or 500 mg/kg of TUDCA every 3 days starting at postnatal day (P) 6, caused significant preservation of cone cell number and cone function at P50. Rods were not protected at P50, but both bilirubin and TUDCA provided modest preservation of ONL thickness and rod function at P30. These data suggest that correlation of serum bilirubin levels with rate of vision loss in patients with retinitis pigmentosa (RP) could provide a useful strategy to test the hypothesis that cones die from oxidative damage in patients with RP. If proof-of-concept is established, manipulation of bilirubin levels and administration of TUDCA could be tested in interventional trials.

PURPOSE. The purpose of this study was to evaluate foveal regeneration and the association between retinal restoration and visual acuity following reattachment surgery for rhegmatogenous retinal detachment (RRD).METHODS. Twenty-nine eyes of 29 patients with successfully reattached macula-off RRD were retrospectively analyzed. We used spectral-domain optical coherence tomography to image macular regions and measure retinal thickness and Snellen chart visual acuity (VA) to evaluate best-corrected VA (BCVA) at 1, 2, 3, 6, 9, and 12 months after vitrectomy. Best-corrected visual acuity data were converted to the logarithm of the minimum angle of resolution scale. Opposite eyes were used as controls.RESULTS. The thicknesses of the external limiting membrane (ELM)-ellipsoid zone (EZ) and EZretinal pigment epithelium (RPE) were significantly thinner in involved eyes than in corresponding unaffected eyes at 1 month after surgery (P < 0.001 for both), and the thickness increased over time (P < 0.001 for both). Best-corrected visual acuity significantly improved over time (P < 0.001), and the improvement correlated with EZ-RPE thickness (r ¼ À0.45, P ¼ 0.021). Multiple regression analysis demonstrated the presence of a foveal bulge as the independent predictor of final BCVA (P < 0.001). Eyes with a foveal bulge had significantly better BCVA and greater EZ-RPE thickness than those without throughout the follow-up period. Significant restoration of the integrity of EZ and cone interdigitation zone (CIZ) was observed over time (P < 0.001 for both) in eyes with a foveal bulge.CONCLUSIONS. The thickness of EZ-RPE and cone density increased during foveal regeneration, as demonstrated by the continuous improvements in CIZ integrity over time, leading to the formation of foveal bulge and good vision following successful reattachment of macula-off RRD.

In retinitis pigmentosa (RP), various mutations cause rod photoreceptor cell death leading to increased oxygen levels in the outer retina, progressive oxidative damage to cones, and gradual loss of cone cell function. We have been exploring the potential of overexpressing components of the endogenous antioxidant defense system to preserve cone cell function in rd10+/+ mice, a model of RP. Rd10+/+ mice deficient in superoxide dismutase 1 (SOD1) showed increased levels of superoxide radicals and carbonyl adducts (a marker of oxidative damage) in the retina, and more rapid loss of cone function than rd10+/+ mice with normal levels of SOD1. This suggests that SOD1 is an important component of the antioxidant defense system of cones, but increased expression of SOD1 in rd10+/+ mice increased oxidative damage and accelerated the loss of cone function. Co-expression of SOD1 with glutathione peroxidase 4 (Gpx4), which like SOD1 is localized in the cytoplasm, but not with catalase targeted to the mitochondria, reduced oxidative damage in the retina and significantly slowed the loss of cone cell function in rd10+/+ mice. Gene transfer resulting in increased expression of SOD2, but not co-expression of SOD2 and mitochondrial Gpx4, resulted in high levels of H2O2 in the retina. These data suggest that in order to provide benefit in RP, over-expression of a SOD must be combined with expression of a peroxide detoxifying enzyme in the same cellular compartment.

To investigate the diurnal variations of the ocular blood flow in healthy eyes using laser speckle flowgraphy (LSFG), and to determine the relationship of the diurnal variations between the ocular blood flow and other ocular parameters.This prospective cross-sectional study was conducted at Nagoya University Hospital. We studied 13 healthy volunteers whose mean age was 33.5 ± 7.6 years. The mean blur rate (MBR), expressing the relative blood flow, on the optic nerve head (ONH) and choroidal blood flow was determined by LSFG (LSFG-NAVI) every 3 hours from 6:00 to 24:00 hours. The intraocular pressure (IOP), choroidal thickness measured by enhanced depth imaging optical coherence tomography, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) in the brachial artery were also recorded. We evaluated the diurnal variations of the parameters and compared the MBR to the other parameters using a linear mixed model.The diurnal variations of the MBR on the ONH varied significantly with a trough at 9:00 hours and a peak at 24:00 hours (P < 0.001, linear mixed model). The MBR of choroid also had significant diurnal variations with a trough at 15:00 hours and a peak at 18:00 hours (P = 0.001). The IOP (P < 0.001), choroidal thickness (P < 0.001), SBP (P = 0.005), DBP (P = 0.001), and HR (P < 0.001) also had significant diurnal variations. Although the diurnal variation of the MBR on the ONH was different from the other parameters, that on the choroid was significantly and positively correlated with the DBP (P = 0.002), mean arterial pressure (P = 0.023), and mean ocular perfusion pressure (P = 0.047).We found significant diurnal variations in the ONH and choroidal blood flow. Although the ONH blood flow had its own diurnal variation because of strong autoregulation, the choroidal blood flow was more likely affected by systemic circulatory factors because of poor autoregulation.