Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1 ؊/؊ mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1 ؊/؊ mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1 ؊/؊ mice showed oxidative damage, and their ␤-cateninmediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1 ؊/؊ mouse is a valuable animal model to study human age-related macular degeneration.animal model ͉ superoxide dismutase A ge-related macular degeneration (AMD) is the leading cause of legal blindness in humans in developed countries (1-5). AMD is characterized by a progressive degeneration of the macula, usually bilateral, leading to a severe decrease in vision and a central scotoma. The decrease in vision results either from retinal degeneration, called geographic atrophy (dry or nonexudative AMD), or from the secondary effects of choroidal neovascularization (CNV; wet or exudative AMD). An early sign of AMD is the appearance of drusen, which are extracellular deposits that accumulate below the retinal pigment epithelium (RPE) and are known to be risk factors for developing CNV (6-8).Mouse models of AMD that manifest some of the features of human AMD have recently begun to appear (9-14); however, most of these mice have only some of the characteristics of human AMD (15). The severity of AMD in humans progresses with increasing age, finally resulting in extensive degeneration of the retina. Therefore, animal models that mimic the complex and progressive characteristics of AMD are needed to investigate the pathogenesis of AMD.Oxidative stress, which refers to cellular or molecular damage caused by reactive oxygen species (ROS), has been implicated in many age-related diseases and aging itself (16,17). ROS include free radicals, hydrogen peroxide, and singlet oxygen and are often the by-products of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, high concentration of polyunsaturated fatty acids, and exposure to light (18). A growing body of evidence suggests that cumulative oxidative damage may be responsible for AMD (18, 19); however, a causative link has not been definitively demonstrated (18).To determine whether there is a causative ro...

The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase (SOD1) in mice leads to many different phenotypes that resemble accelerated aging. The purpose of this study was to examine the morphology and physiology of the sensory retina in Sod1 ؊/؊ mice. The amplitudes of the a-and b-waves of electroretinograms elicited by stimuli of different intensity were reduced in senescent Sod1 ؊/؊ mice, and this reduction in amplitude was more pronounced with increasing age. Retinal morphometric analyses showed a reduced number of nuclei in both the inner nuclear cell layer and outer nuclear cell layer. Electron microscopy revealed swollen cells and degenerated mitochondria in the inner nuclear cell and outer nuclear cell layer of senescent Sod1 ؊/؊ mice indicating necrotic cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed no significant differences in the number of apoptotic cells between Sod1 ؊/؊ and wild-type mice, and activated caspase-3 could not be detected in the retina of Sod1 ؊/؊ mice. In addition to the age-related macular degeneration-like phenotypes previously reported, Sod1 ؊/؊ mice also present progressive retinal degeneration. Our results indicate that Sod1 ؊/؊ mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated retinal degeneration. The superoxide dismutase (SOD) family is one of the main antioxidant systems in the body and is made up of the three SOD isoenzymes; Cu,Zn-superoxide dismutase (SOD1) exists in the cytoplasm, SOD2 or Mn-SOD in the mitochondrial matrix, and SOD3 or extracellular SOD in the interstitium of tissues as the secreted form.1 SOD1 catalyzes superoxide radical dismutation and is distributed throughout the body, 1 and among the three isozymes, it is the most abundant in the retina.2 This suggests that SOD1 may be important in protecting the sensory retina from the reactive oxygen species (ROS)-mediated retinal damage.Many models of retinal degeneration have been studied 3,4 ; however, the mechanism of retinal cell deaths in some of these models has still not been determined. Cell death can be either necrotic or apoptotic, and necrotic cell death is characterized by a swelling of the cell membranes and organelles that leads to a disruption of the cell membranes and lysis. These alterations subsequently lead to inflammatory responses. 5 Apoptosis is a process of programmed cell death, and involves an orchestrated series of biochemical events leading to characteristic cell morphology and death. In some models of retinal degeneration, the death of the neurons has been shown to be attributable to apoptosis. 6 -8 SOD1 deficiency (Sod1 Ϫ/Ϫ ) leads to many different phenotypes resembling aging, and the changes are attributable to an elevation of ROS. 9,10 We recently reported that senescent Sod1 Ϫ/Ϫ mice had features of age-related macular degeneration (AMD) including the presence of drusen, choroidal neovascularization, and retinal pigment epithelium d...

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Chronic subdural hematoma is a common disease. Occasionally, however, it is so puzzling to make a diagnosis clearly and immediately, that the delay of the manage ment may occur. So the purpose of this paper is to clarify the general picture of chronic subdural hematoma from a statistical analysis in 309 adult cases. Through this survey the role of trauma as the triggering factor is to be checked and the signs and symptoms will be summarized and divided into groups according to clinical features, which will make the diagnosis easy and useful to dissolve the pitfall. Pathophysiology and dy namics of the capsule of the hematoma are investigated in some cases, and the dys function of the liver is also inquired. Follow-up study was performed, which will con tribute to the selection of the operative method. Materials and Methods Statistical Analysis History of Trauma History of trauma preceeding the onset of the disease was noted in 276 cases (89%), in which were the traffic accidents 47%, ordinary life 35%, sport accidents 10 %, industry accidents 3 %, and so on (Table 1). In sport accidents 9 cases were