Intraocular fluid antibody quotients following inoculation with two different antigens in experimental herpes simplex virus retinochoroiditis

Viral retinochoroiditis was induced experimentally by inoculation of herpes simplex virus into the vitreous body in rabbits. The animals were sensitized systemically using 2 pathogens as antigens (herpes simplex virus and toxoplasma gondii) 3 weeks prior to intraocular inoculation. Serum and intraocular fluid were collected 2 weeks after inoculation. The intraocular fluid antibody titers and quotients for these 2 pathogens were then measured to determine the effects of serum antibodies, which are thought to enter the eyes as a result of destruction of the blood-ocular barrier. Experimental criteria for antibody quotients were also determined. Antibody quotients for the etiological virus (herpes simplex virus) ranged from 2 to 20, with an average of 9.7. Those for toxoplasma gondii, the antibody of which is thought to enter the eye from the blood, were all less than 5 with average of 1.9. From these results, it would seem that when the antibody quotient of a pathogen in more than 6 in the intraocular fluid, it is likely to be an etiological organism, while the possibility of infection is very low when the quotient is under 2. More precise studies are required to identify an etiological pathogen when the quotient is 2-6.     

Association of antibody titer and chorioretinal scarring in toxoplasmosis retinochoroiditis

Thirty subjects with clinically diagnosed toxoplasmosis retinal lesions, and 30 control subjects matched for age, sex, and race, were evaluated for the presence of IgG antitoxoplasmosis antibodies by enzyme-linked immunosorbent assay (ELISA) methodology. Positive titer was found in 56% of subjects and 20% of controls. Positivity of titer was not correlated to location of lesion, laterality, presence of satellites, sex, or race. Increasing age in both subjects and controls was weakly correlated to positive titer. Study results indicate that a relative overdiagnosis of toxoplasmosis occurs if positive antibody titer is accepted as criteria for positive diagnosis. Currently employed criteria based on physical findings appear to be of little value in predicting positive titer.     

Latent infections by herpes simplex virus in experimental animals

Studies in experimental animals, initially the rabbit and more recently the mouse, have been of great importance in establishing present day concepts concerning the phenomenon of herpesvirus latency. These early observations coupled with more recent knowledge of virological consequences following surgical manipulation of the trigeminal tract have led to a general hypothesis for the natural history of herpetic infections: The infection follows a circuit from skin, mucous membrane, or eye (the primary infection) to the corresponding sensory ganglia via associated nerves. Virus becomes latent in the ganglia and later, as a result of one of the many provocations known to be associated with recurrence of herpetic lesions, is reactivated and travels via the nerve to the surface and again produces lesions. Current research investigating this hypothesis is reviewed.     

小鼠单纯疱疹病毒性角膜炎中基质金属蛋白酶的表达及活性研究

目的 探讨角膜感染Ⅰ型单纯疱疹病毒(HSV-1)后基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)在角膜中的分布及酶活性表达。方法 BALB／c小鼠眼角膜接种HSV-1(KOS株)以诱发单纯疱疹病毒性角膜炎(HSK)。分别收集正常眼球及感染后第2、7、14及28天的感染眼球。应用免疫组织化学法和Western blot方法检测MMP-2、-8、-9及TIMP-1、-2在角膜组织中的表达,并应用酶谱(Zymography)技术检测MMPs的酶活性。结果 感染后第2天,感染眼的MMP-2、-9及TIMP-1、-2表达比未感染眼增加且表达主要位于浅表基质层及上皮下的炎性细胞中。感染后第14和28天可见坏死性角膜炎及角膜溃疡形成,同时角膜基质和浸润的炎性细胞中尤其溃疡处,可见MMP-2、-9及TIMP-1、-2表达显著增加。溃疡区域有大量MMP-8阳性染色的中性粒细胞。角膜感染HSV-1后,明胶酶(MMP-2、-9)活性和胶原酶(MMP-8)活性均增强。结论 HSV-1角膜感染后,由角膜细胞和浸润的炎性细胞分泌产生的MMPs可能对上皮性角膜炎与溃疡形成过程起重要的促进作用。MMPs与TIMPs的相互作用可能对HSK的坏死性病变起重要调节作用。（中华眼科杂志,2004,40：395-399)     

基质金属蛋白酶在实验性单纯疱疹性角膜炎中的分布表达

目的 明确角膜感染Ⅰ型单纯疱疹病毒(HSV—1)后基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)在角膜中的分布。方法 HSV—1(KOS株)接种于BALB／c小鼠角膜上。分别收集正常眼球及感染后第2、7、14及28d的感染眼球行石蜡包埋，并应用抗MMP—2、—8、—9及TIMP—1、—2的抗体免疫染色角膜切片。结果 感染后第2d，MMP—2、—9及TIMP—1、—2的表达比未感染眼增加且表达主要位于浅表基质层及上皮下的炎性细胞中。感染后第14d及28d可见坏死性角膜炎及角膜溃疡形成，角膜基质中及浸润的炎性细胞中尤其是溃疡处可见MMP—2、—9及TIMP—1、—2表达显著增加。溃疡区域可见大量MMP—8阳性染色的中性粒细胞。结论 HSV—1角膜感染后由角膜细胞及浸润的炎性细胞分泌产生的MMPs对于上皮性角膜炎及溃疡形成过程可能起重要作用。     

Optic nerve finding in experimental retinitis induced by herpes simplex virus

We reported histological changes and viral localization of HSV-1 in the optic nerve by the ABC-method and electron microscopy, after intravitreal inoculation. There was neither histological change nor antigen deposition on the specimen of 3 days after inoculation. Some series of antigen-positive sites were successively found along the nerve fiber from the lamina cribrosa to the optic chiasma in the optic nerve on 4 days after inoculation. Round cell infiltration were also found around these sites, and these changes increased on the 8th day. Antigen-positive cells were mainly considered to be oligodendroglia and astrocytes. These results suggested that HSV-1 infected the optic nerve fiber via the retina. On the way to be the brain by axonal transport, they would infiltrate to the glial cells, where they could replicate and spread to neighbouring glial cells.     

Effect of experimental herpes simplex virus vaccine on established ganglionic latency

Mice were inoculated with herpes simplex virus type 1 by the corneal route beforehand. Ten weeks after the inoculation, one group of mice was repeatedly treated with infectious virus-free, detergent-soluble extract of virus-infected cells (DSE) by the intraperitoneal route and the other group served as the controls. The virus recovery rate from the trigeminal ganglia of DES-treated mice was markedly reduced as compared with that of untreated mice, when a small amount of inocula was used. However, no significant decrease in the virus recovery rate was obtained when a large amount of inocula was used, suggesting that treatment with DSE had a limited effect on established ganglionic latency. The level of neutralizing antibody titers in the serum did not seem to be correlated with the efficacy of DSE in mice infected with a small amount of inocula.     

Histopathologic characteristics of two forms of experimental herpes simplex virus retinitis

Herpes simplex virus type 1 (HSV-1) inoculated intracamerally into one anterior chamber of a BALB/c mouse produces retinitis in the uninoculated contralateral eye within 7 to 10 days while the retina of the inoculated eye is spared. In sharp contrast, animals receiving HSV type 2 (HSV-2) by the anterior chamber route develop a dramatic retinitis in the inoculated eye by day 7 postinoculation while the retina of the contralateral eye remains uninvolved. Histopathologic examination of retinal destruction in the HSV-2-infected ipsilateral eye revealed features which were distinct from those observed in the contralateral eye of HSV-1-infected animals. Whereas HSV-1 produced a rapid, explosive, retinitis which led to destruction of all cell layers of the contralateral retina, HSV-2 induced a retinitis in the ipsilateral eye that was more gradual in onset. Ipsilateral HSV-2 retinitis was characterized initially by disruption of the ganglion and inner nuclear layers which progressed by day 10 to 14 to complete replacement of the retina by a fibrocellular scar. These changes were dominated by a vigorous mononuclear cell infiltrate, a feature not observed in the HSV-1-infected contralateral retinitis. These results suggest that experimental retinitides produced by HSV-1 and HSV-2 are of diverse pathogenesis.     

单纯疱疹病毒侵入受体在单纯疱疹病毒性角膜炎发病机制中的作用

单纯疱疹病毒侵入受体(疱疹病毒侵入介质、连接素-1、连接素-2、3-O-硫酸化的硫酸乙酰肝素等)是单纯疱疹病毒(HSV)侵入细胞及在细胞间扩散所必需的物质.不同的受体对HSV在组织的感染和扩散中具有不同的作用.疱疹病毒侵入介质可介导HSV进入小梁网细胞、结膜上皮细胞和角膜成纤维细胞,连接素则介导HSV侵入神经组织和细胞...     

Scanning electron microscope study of herpes simplex virus experimental disciform keratitis.

Scanning electron microscopy of the endothelium of experimental disciform keratitis revealed corneal endothelial changes which distinguished disciform oedema from the more progressive stages of disciform keratitis. The endothelium of corneas with disciform oedema were wholly intact and characterised by subtle morphological alterations. In contrast, the more progressive stages of disciform keratitis were characterised by massive destruction and denudation of the endothelium. The significance of these observations is discussed.     

Intraocular antibody synthesis during experimental uveitis

Determination of intraocular antibody synthesis against certain microorganisms is a diagnostic aid in identifying the causative agent in clinical uveitis. Little is known, however, concerning the kinetics and specificity of antibodies produced during intraocular inflammation. To investigate this subject we induced uveitis in rabbits by injecting small amounts of human serum albumin (HSA) into the vitreous. Aqueous humor and serum were taken before and after the induction of uveitis and levels of total IgG, rabbit albumin and anti-HSA-IgG were determined. The anti-HSA-IgG was quantitated using immunoaffinity purified anti-HSA-IgG as a standard. Six weeks after intravitreal HSA injection, high levels of total IgG (4.7 mg/ml) and albumin (15.4 mg/ml) were observed in the aqueous as compared to control eyes (IgG: 0.12 mg/ml; albumin: 0.48 mg/ml). Using albumin to correct for blood aqueous barrier breakdown we calculated that only 0.6% of the locally synthesized IgG was directed against intravitreally injected HSA. Two months after the intravitreal injection of HSA the main signs of the uveitis had subsided. A recurrent uveitis was subsequently induced by an intravenous HSA injection. This resulted in a marked increase of total IgG (14.3 mg/ml) and albumin (24.6 mg/ml) in the aqueous humor of the uveitis eyes. It was remarkable that the mean anti-HSA-IgG level (0.62 mg/ml) in the uveitis eyes was higher than that seen in serum (0.41 mg/ml). After this secondary uveitis, 9% of the locally synthesized antibodies were directed against HSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

单纯疱疹病毒性角膜炎的研究新进展

单纯疱疹病毒性角膜炎是一种重要的致盲性眼病。它的致盲性和治疗上的困难性在于它的反复发作,从而引起角膜混浊,最终导致视力的丧失。随着分子生物学的发展,目前对于单纯疱疹病毒性角膜炎的诊断有着突飞猛进的发展,然而对于治疗复发性单纯疱疹病毒性角膜炎却没有有效药物,这将有待于分子生物学、病毒学、传统中医与现代西医的共同努力。     

Histopathology of herpes simplex virus keratouveitis

Twenty-four eyes removed for complications of HSV keratitis were studied histopathologically. There were 20 men and 4 women with an average age of 61 years. Severe keratitis was seen in 14, moderate in 7, and mild in 3 eyes. Common features associated with severe keratitis were: acute perforation, granulomatous keratitis with giant cells in the stroma and Descemet's region, stromal inflammatory cells, angle-closure, severe iridocyclitis with diffuse or focal infiltration of lymphocytes and plasma cells, low-grade vitritis, choroiditis, and/or retinal periphlebitis. Specimens with moderate to mild keratitis had a similar distribution of inflammation but a lower incidence of granulomatous keratitis.     

Ocular pathogenicity of herpes simplex virus

As a relatively small, discrete organ that contains a number of widely different cell types the eye provides an intriguing system in which to study fundamental aspects of virus/cell interactions. Such aspects are considered with particular reference to herpes simplex virus and the pivotal role of virus/neuron interactions in the development of ocular disease. Three aspects of this interaction are discussed: the entry of virus into the eye latency in the trigeminal ganglion nerve damage.     

Type 2 herpes simplex virus infections

The problems related to herpes simplex virus (HSV) type 2 infections include: (1) the clinical diseases produced primarily at urogenital sites, but also in extragenital areas, and the frequent recurrences of such infections; (2) the severity of the diseases produced in immunocompromised hosts and in newborns, including a variety of ocular manifestations; and (3) the possible role of the virus in human cancers. The usually sexually transmitted mode of spread of this virus has increased current medical concern with this virus. Altthough laboratory diagnosis of HSV-2 infection is currently available, we still lack effective preventive or therapeutic means for most clinical forms of the infection. However, the great progress made over the past decade in the molecular, virological, immunological and clinicoepidemiological aspects of HSV are providing the necessary tools to attain this goal.