Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively activated M2 macrophages and ameliorates insulin resistance and fatty liver in lipoatrophic diabetic A-ZIP transgenic mice.

AIMS/HYPOTHESIS: Monocyte chemoattractant protein-1 (MCP-1)/chemokine (C-C motif) ligand (CCL) 2 (CCL2) secreted from white adipose tissue (WAT) in obesity has been reported to contribute to tissue macrophage accumulation and insulin resistance by inducing a chronic inflammatory state. MCP-1 has been shown to be elevated in the fatty liver of lipoatrophic A-ZIP-transgenic (A-ZIP-Tg) mice. Treatment of these mice with the CC chemokine receptor (CCR) 2 antagonist has been shown to ameliorate the hyperglycaemia, hyperinsulinaemia and hepatomegaly, in conjunction with reducing liver inflammation. However, since CCR2 antagonists can block not only MCP-1 but also MCP-2 (CCL8) and MCP-3 (CCL7), it remains unclear whether MCP-1 secreted from the liver could contribute to hyperglycaemia, hyperinsulinaemia and hepatomegaly in conjunction with liver inflammation, as well as to the M1 and M2 states of macrophage polarisation. METHODS: To address these issues, we analysed the effects of targeted disruption of MCP-1 in A-ZIP-Tg mice. RESULTS: MCP-1 deficiency alone or per se resulted in a significant amelioration of insulin resistance in A-ZIP-Tg mice, which was associated with a suppression of extracellular signal-regulated protein kinase (ERK)-1/2 and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation in liver. Although MCP-1 deficiency did not reduce the expression of macrophage markers, it increased the expression of the genes encoding M2 macrophage markers such as Arg1 and Chi3l3, as well as significantly reducing the triacylglycerol content of livers from A-ZIP-Tg mice. CONCLUSIONS/ INTERPRETATION: Our data clearly indicated that MCP-1 deficiency improved insulin resistance and hepatic steatosis in A-ZIP-Tg mice and was associated with switching macrophage polarisation and suppressing ERK-1/2 and p38MAPK phosphorylation.

Visual deprivation myopia with translucent and black goggles.

To study how different visual deprivation conditions influence the degree of myopia, chicks were reared under conditions of unilateral and bilateral visual deprivation with translucent and black goggles in environments of a 12-hour light/dark cycle and complete darkness. Two weeks after hatching, the refractive errors and axial lengths of the eyes were measured. The deprived eyes of the light/dark-reared chicks exhibited severe myopia both unilaterally and bilaterally as well as axial elongations. The dark-reared chicks exhibited slight myopia in the eyes with goggles and no significant axial elongation. The experiments suggest that different degrees of visual deprivation can also cause severe myopia, that myopia develops independently in each eye, and that a light/dark environment is required for severe myopia to develop.

A clinical study of the development of posterior vitreous detachment in high myopia.

PURPOSE: The correlation of age, axial length, and myopic chorioretinal atrophy with vitreous changes in high myopia were analyzed to investigate the development of posterior vitreous detachment (PVD) in high myopia. METHODS: The vitreous condition of 329 consecutive eyes with high myopia (more than -8.25 diopters (D) and more than 26.0 mm of axial length) was examined biomicroscopically with a +90-D preset lens and a Goldmann three-mirror contact lens. RESULTS: The prevalence of PVD in high myopia was 12.5% in patients between 20 and 29 years of age, and it increased with age. The incidence of PVD in eyes with axial length of more than 30.0 mm was 60.7% and was statistically higher than the prevalence in eyes with an axial length of less than 29.9 mm (P < 0.01). Multiple logistic regression analysis showed that age and axial length were statistically significant factors in the development of PVD and lacuna formation in high myopia (P < 0.01), but the influence of chorioretinal atrophy was not significant. CONCLUSION: The results of this study suggest that liquefaction of the vitreous begins at a relatively young age in patients with high myopia and progresses with age and axial elongation, thus resulting in a frequent occurrence of PVD.

Histopathologic examination of vascular patterns in subfoveal neovascular membranes.

BACKGROUND: Subfoveal neovascular membranes cause significant visual loss in age-related macular degeneration (AMD) and the ocular histoplasmosis syndrome. The frequency of post-laser treatment persistence or recurrence of subfoveal membranes in AMD is as high as 51%. The reason for the high incidence of failure after laser treatment is unknown. The authors performed a histopathologic study of subfoveal membranes to determine the distribution of blood vessels within the neovascular complex, and to see if the blood vessel pattern would provide insight into the reason for laser treatment failure. METHODS: The authors used light microscopy to examine serial sections of subfoveal membranes from six patients (4 with AMD, 2 with the ocular histoplasmosis syndrome). The data from this examination were used to create detailed two-dimensional vascular maps of each membrane. RESULTS: The authors found that subfoveal membranes from patients with AMD and the ocular histoplasmosis syndrome, whether occurring de novo or after laser treatment, have a nonuniform distribution of blood vessels, and that large areas which include the membrane margin may be avascular. CONCLUSIONS: Using current laser treatment protocols, it is likely that avascular or poorly perfused peripheral areas of the neovascular complex would be left untreated after laser photocoagulation. Partial treatment of the neovascular complex may contribute to the high rate of post-laser treatment persistence or recurrence of subfoveal membranes.

Clinicopathologic correlation of a macular hole treated by cortical vitreous peeling and gas tamponade.

PURPOSE: To study the histopathology of a stage III macular hole that had been treated by vitrectomy with cortical vitreous and epicortical vitreous membrane peeling and gas tamponade. METHODS: The light and electron microscopic features of a treated macular hole were studied. RESULTS: A 16-microns-wide break was present in the external limiting membrane. This was sealed by Müller cell processes. Photoreceptors adjacent to the healed defect appeared normal. No cystoid macular edema was present. CONCLUSION: Cortical vitreous peeling and gas tamponade can allow the macular hole to settle and the edges to re-approximate. The residual defect can be sealed by Müller cells.

Ocular pulse and pulsatile change of scleral strain in living in situ rabbit eyes.

We investigated ocular pulse (OP), pulsatile change of scleral strain (PSS), and intraocular pressure (IOP) to evaluate extensibility of the sclera in seven living rabbit eyes. OP and IOP were measured by a semiconductor pressure transducer and PSS was measured using a small foil strain gauge. Both OP and PSS generated similar bell-shaped curves in relation to IOP. Between OP and PSS, there was a linear relation, the gradient of which was considered to be an index of the modulus of elasticity of the sclera. With further refinement of the method, it is possible to apply this technique to human eyes.

Intraocular gnathostomiasis.

The clinical and histologic features of an intraocular parasite from a 29-year-old woman are reported. The live organism was located in the posterior vitreous near the optic disc and was successfully removed by vitreous aspiration. The parasite was identified as an advanced stage larvae of Gnathostoma spinigerum. This is the first case report of the scanning electron microscopic findings of intraocular gnathostomiasis. The features of nine previously reported cases of intraocular gnathostomiasis are reviewed.

Recurrence of nanophthalmic uveal effusion.

A patient with nanophthalmic uveal effusion had a recurrence 7 months after the initial sclerectomies and sclerostomies. The effusion was cured by repeating the procedure. Specimens obtained at the first operation showed interlacing collagen lamellae and thin collagen bundles with an electron-dense deposit in the perifibrillar space. Specimens from the second operation showed disarranged collagen bundles with closely packed thin collagen fibrils. Collagen lamellae were not found. The regenerated scleral tissue was thought to interfere with the transscleral outflow and to block the bypass route, thus resulting in the recurrence of uveal effusion.

Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade.

The clinicopathologic findings of light and electron microscopic examination of a 78-year-old woman who underwent successful bilateral pars plana vitrectomy for bilateral stage III macular holes are reported. Examination disclosed anatomical repair of the full-thickness macular holes by glial cell proliferation in the left eye. The hole apparently collapsed with no glial cell proliferation in the right eye. The photoreceptors adjacent to the healed macular holes appeared normal. Defects in the internal limiting membrane in the foveal area were noted in both eyes.

[Electron microscopic study of the choroidal melanocytes and elastic fibers].

The relationship between choroidal melanocytes and elastic fibers as well as collagen fibers was studied by electron microscopy. In pigmented rabbits (Dutch rabbits), the choroidal melanocytes were distributed mainly at the suprachoroidea and formed layers alternating with fibroblasts. The elastic fibers and oxytaran fibers were in close proximity to the melanocytes and their cytoplasmic processes aligned along the long axis of the elastic fibers. Furthermore, the bundles of the collagen fibers were engulfed by the melanocytes. The present findings suggest that the choroidal melanocytes have a close relationship with the elastic fibers, as has been reported with dermal melanocytes and elastic fibers.

Scleral change in experimentally myopic monkeys.

To elucidate changes in the sclera of myopic eyes free of other obvious pathological features, morphometric and ultrastructural studies on the posterior sclera at the foveola of the three lid-fused monkeys that had developed high myopia were performed. The myopic eyes showed increased axial length, and their scleral thickness was about half that of the control eyes. Furthermore, a gradual increase in the size of collagen bundles and fibrils from the inner to the outer layer of the sclera was observed in the control eyes, but was not evident in the myopic eyes. From the present study, it can be speculated that an alteration of fibrillogenesis in the sclera is a key feature of scleral thinning in lid-suture myopia, and that axial elongation of the eyeball results from a combination of altered fibrillogenesis and mechanical expansion.

An analysis of subretinal fluid in bullous retinal detachment.

A patient with bilateral bullous retinal detachment underwent drainage of the subretinal fluid. The analysis of the subretinal fluid revealed a high protein concentration--17.4 g/dl OD, 27.5 g/dl OS--which was 3-5 times higher than that of the patient's serum. The protein fractionations of the subretinal fluid were almost the same as those of the serum. These findings may well explain the shifting fluid and support the theory that bullous retinal detachment is caused by the breakdown of retinal pigment epithelial function as a barrier between the choroid and retina.

Influence of intraocular pressure on axial elongation.

The role of intraocular pressure (IOP) on axial elongation was studied by the following three experiments. 1) Thickness of the sclera in the lid-sutured-myopia of three monkeys was examined by light microscopy. The sclera of the experimental eye in the posterior pole was thinner than that of the control eye, but no differences were found in the equatorial and limbal parts of the sclera. 2) By increasing IOP, the scleral wall extensibility in 8 normal, enucleated rabbit eyes was measured by placing the foil strain gauges on the sclera. Extensibility of the sclera in the posterior pole showed a different response from that at the equator and in the limbus. 3) IOPs of the 184 human myopic eyes were measured by a Mackay-Marg tonometer in various postures. IOP elevations in high myopia and postural variations of IOP were obtained. From these experiments, it was suggested that IOP seemed to be one of the main factors in increasing the axis to the posterior pole.

A study of experimental cyanide encephalopathy in the acute phase--physiological and neuropathological correlation.

A study was performed to elucidate the significance of various physiological factors contributing to the pathogenesis of experimental cyanide encephalopathy, such as the systemic arterial blood pressure, venous pressure, common carotid blood flow and local blood flow of the cerebral grey and white matters, and blood gas including pH. The histology and topography of the brain damage was also analysed. Twenty-one cats were divided into four groups. The animals in groups 1, 2 and 3 were subjected to continuous infusion of 0.2% sodium cyanide solution and to the ensuing hypotension below 100 mm Hg by administering a ganglion-blocking drug and by respiratory arrest. Severe damage developed in the deep cerebral white matter, corpus callosum, pallidum and substantia nigra, but the damage of the cerebral cortex and hippocampus was not remarkable. The animals in group 4 that were subjected to cyanide infusion without significant hypotension (above 100 mm Hg), but to the same degree of acidosis as that of the other groups, had similar morphological changes, but to a lesser degree. On the basis of our physiological and morphological findings, we speculated that the pathophysiological factors of tissue hypoxia and subsequent hypotension operated in cyanide leucoencephalopathy. The topographic selectivity seemed to be related to the characteristic cerebral vascular system, and the severity of the white matter lesions was related to the intensity of both hypoxia and hypotension during cyanide infusion, but not to the extent of acidosis, total dose of cyanide or duration of its infusion per se.