Uninoculated Eye Research Articles

Neural pathogenesis of experimental scrapie after intraocular inoculation of hamsters

Hamsters were inoculated intravitreally with the scrapie agent. All animals developed scrapie and retinal degeneration typical of scrapie. The retinal degeneration was greater in the inoculated eyes than in the uninoculated eyes. Replication of the scrapie agent was rapid in the inoculated eye. Infectivity then spread slowly down the ipsilateral optic nerve to the brain. The replication in the brain paralleled that in the retina of the uninoculated eye. The results support a neural spread of scrapie.

Retrobulbar administration of steroids in herpes simplex uveitis. Efficacy of treatment in rabbits.

Efficacy of retrobulbar injections of dexamethasone on the von Szily model of herpes simplex chorioretinitis was tested in rabbits. Herpesvirus hominis was injected into the anterior chamber of one eye of 45 rabbits. In each, a uveitis developed in the injected eye. In 36 animals a chorioretinitis appeared 7 to 12 days later in the uninoculated eye. Retrobulbar steroid or placebo therapy was begun in matched animals after clinical signs of posterior chorioretinitis appeared. Eyes were examined daily by an observer not informed of the nature of the treatment. Clinical changes were correlated with photographs, viral titrations, and histologic examinations. A definite anti-inflammatory effect was observed during a short course of retrobulbar steroid therapy, although the final outcome was not altered. This short-term clinical improvement occurred without any significant increase in virus multiplication.

The effect of trachoma virus vaccine on the course of experimental trachoma infection in blind human volunteers.

The TRIC-Taiwan-1-1958 strain of elementary body virus isolated from a trachoma patient on Taiwan has been proven capable of reproducing trachoma by experimental inoculation of six human volunteers. Virus material derived from the seventh passage in embryonated hen eggs caused the clinical picture of trachoma in every inoculation, even at the dilution of 10(-4) of infected yolk sacs (approximately 1 EID(50)). There was a similar clinical picture with each inoculation beginning with an acute follicular conjunctivitis which progressed for 4 months and then persisted with chronic changes until 9 months when treatment was begun. The illness was generally more acute than would be expected in natural trachoma. That trachoma was reproduced was shown by the involvement of the cornea with epithelial keratitis and pannus, and by the occurrence of gelatinous follicles and eventual cicatrization of the conjunctiva. These clinical findings were supported by repeated demonstrations of typical inclusion bodies of Halberstaedter-Prowazek from conjunctival and even corneal cells, by repeated reisolation of elementary body virus in egg yolk sacs, and by the development of complement-fixing antibody with a "specific" trachoma antigen in each volunteer. Control inoculations with adenovirus type 4 and normal yolk sac showed different clinical and laboratory findings. Experimental trachoma vaccine was given to three of the volunteers to study its effect on the course of illness. An antibody response to the vaccine was demonstrated and there was a modification of disease in the volunteers receiving vaccine. While the three volunteers who received placebo each developed cross-infection of their uninoculated eye and had an acute reactivation of the bilateral disease after 1 to 2 months of antibiotic eye ointment therapy, the vaccinated volunteers remained free of infection in uninoculated eyes and showed no relapse after ointment therapy. Treatment with sulfamethoxypyridazine, a sulfa drug with prolonged action, proved to be an effective and relatively simple method of therapy for experimental trachoma.

Studies on the Infectivity of Trachoma : X. Frequency and Distribution of the Inclusion Body and its Possible Relation to Pathogenesis

The occurrence of follicles has been observed to follow the transfer of trachomatous material to the conjunctiva of monkeys. The experimental infection is preceded by an incubation period of several days to a month. The follicles frequently extend to the uninoculated eye. The infection persists for a few weeks to many months, but without exhibiting scar-tissue formation or corneal involvement. The histological changes accompanying the infection consist chiefly of follicles composed of small lymphocytes and plasma cells surrounded by a layer of fibroblasts. Material obtained from human trachoma varies greatly in infectivity for monkeys. Thus of 62 tissues from active trachoma studied, only 41 were infectious. Similarly, there is a great variation in individual susceptibility of monkeys to infection, but it is felt that the resistance observed in certain animals is relative and not absolute. The infectivity of a given tissue does not appear to be related to the presence or absence of epithelial inclusions in the tissue used for inoculation. Similarly, frequent examinations of infected monkeys failed to reveal the presence of inclusions. Attempts to establish the disease permanently in monkeys by serial passage from animal to animal were unsuccessful. The infectious agent was usually lost by the third animal-to-animal transfer. Recovery from the experimental disease did not affect the course nor character of later infection by the same agent. It has been possible to induce the disease 2 and 3 times successfully in the same animals, thus indicating a complete inability of the monkey to establish an immunity to the infection. On the other hand, recurrence of the disease was not stimulated by a variety of nonspecific agents. From the Bacteriological Laboratories of the Oscar Johnson Institute, Washington University, School of Medicine, Saint Louis, Missouri. The entire work was conducted under a grant from the Commonwealth Fund of New York City.

Studies on the Infectivity of Trachoma: I. the Transfer of a Conjunctival Infection to Monkeys by Means of Trachomatous Tissues

The occurrence of follicles has been observed to follow the transfer of trachomatous material to the conjunctiva of monkeys. The experimental infection is preceded by an incubation period of several days to a month. The follicles frequently extend to the uninoculated eye. The infection persists for a few weeks to many months, but without exhibiting scar-tissue formation or corneal involvement. The histological changes accompanying the infection consist chiefly of follicles composed of small lymphocytes and plasma cells surrounded by a layer of fibroblasts. Material obtained from human trachoma varies greatly in infectivity for monkeys. Thus of 62 tissues from active trachoma studied, only 41 were infectious. Similarly, there is a great variation in individual susceptibility of monkeys to infection, but it is felt that the resistance observed in certain animals is relative and not absolute. The infectivity of a given tissue does not appear to be related to the presence or absence of epithelial inclusions in the tissue used for inoculation. Similarly, frequent examinations of infected monkeys failed to reveal the presence of inclusions. Attempts to establish the disease permanently in monkeys by serial passage from animal to animal were unsuccessful. The infectious agent was usually lost by the third animal-to-animal transfer. Recovery from the experimental disease did not affect the course nor character of later infection by the same agent. It has been possible to induce the disease 2 and 3 times successfully in the same animals, thus indicating a complete inability of the monkey to establish an immunity to the infection. On the other hand, recurrence of the disease was not stimulated by a variety of nonspecific agents. From the Bacteriological Laboratories of the Oscar Johnson Institute, Washington University, School of Medicine, Saint Louis, Missouri. The entire work was conducted under a grant from the Commonwealth Fund of New York City.

The Influence of Dietary Deficiency on the Transmissibility of Trachoma to Monkeys

The influence of dietary deficiency on the transmissibility of trachoma to monkeys was studied. Twenty-two malnourished monkeys were inoculated with fresh trachomatous material; follicular changes developed in the inoculated eyes in seventeen monkeys after a period of 16-37 days and persisted for 17-90 days. There was no transfer of the process to the uninoculated eye. In 15 well-nourished monkeys inoculated by the same technic, follicular changes developed in 13 after a period of 8-30 days, spread to the uninoculated eye, and persisted for 5-10 months. Neither macroscopic scarring of the conjunctiva nor corneal involvement occurred in either series. Diets low in vitamins, low in protein, and high in fats were used. From the Oscar Johnson Institute, Washington University, School of Medicine, Saint Louis, Missouri. Conducted under a grant from the Commonwealth Fund of New York. The influence of dietary deficiency on the transmissibility of trachoma to monkeys was studied. Twenty-two malnourished monkeys were inoculated with fresh trachomatous material; follicular changes developed in the inoculated eyes in seventeen monkeys after a period of 16-37 days and persisted for 17-90 days. There was no transfer of the process to the uninoculated eye. In 15 well-nourished monkeys inoculated by the same technic, follicular changes developed in 13 after a period of 8-30 days, spread to the uninoculated eye, and persisted for 5-10 months. Neither macroscopic scarring of the conjunctiva nor corneal involvement occurred in either series. Diets low in vitamins, low in protein, and high in fats were used. From the Oscar Johnson Institute, Washington University, School of Medicine, Saint Louis, Missouri. Conducted under a grant from the Commonwealth Fund of New York.

Studies on Vascularization of the Cornea

Summary and Conclusions Repeated inoculations of Staphylococcus aureus by corneal scarification and conjunctival instillation, stimulate clouding and vascularization of the cornea of monkeys, (M. rhesus). Similar inoculations of monkeys with Bact. granulsosis apparently do not induce corneal reactivity under conditions favorable for stimulating reactivity to Staphylococcus. Repeated intracorneal injections of crystalline egg albumin also stimulate clouding and vascularization of the cornea. Corneal reactivity of the uninoculated eye as well as heightened skin reactivity does not occur under the conditions stated above. No specific antibodies are detectable in the serum of monkeys inoculated as described in this report. Certain contrasts in corneal vascularity induced under similar conditions in the rabbit and monkey are indicated.

Studies on Vascularization of the Cornea

Summary and Conclusions Vascularization of the cornea of rabbits has been studied as a response to bacterial hypersensitiveness. The organisms utilized for inducing hypersensitiveness have been Staphylococcus aureus, Pneumococcus and Bact. granulosis. These bacteria have been administered repeatedly by intracutaneous and sub-conjunctival injections: By conjunctival instillations; a, without corneal scarification; b, with corneal scarification; c, with mixtures of broth cultures and sand; and d, by preliminary instillation of homologous broth filtrates a day preceding the administration of bacteria. Staphylococcus aureus has been the most consistent sensitizing antigen, and instillation with corneal scarification, the most effective method of inducing vascularization of the cornea. Direct corneal vascularization occurs only when the cornea is injured slightly but definitely, but similar trauma per se does not cause this reaction. The corneal vascularity observed during early development resembled pannus tenuis of trachoma, and that observed in the latter stages was suggestive of pannus crassus. It was not possible to correlate corneal sensitivity of the inoculated eye with the presence or absence of corneal sensitivity of the uninoculated eye or to heightened skin reactivity to the homologous bacterial nucleoprotein, or to the presence or absence of circulating antibodies. The antibody response following conjunctival instillations in its various forms was slight or entirely lacking. While the indications are that the vascularity described in this study is in response to bacterial hypersensitiveness, no experiments have been undertaken as yet to indicate whether pannus in trachoma is initiated by a similar stimulus.

Studies on Trachoma

Summary and Conclusions By repeated irritation with an alkaline dust (Portland cement) or by previous infection with a virulent hemoglobinophilic bacillus, the monkey's conjunctiva was at times rendered more vulnerable to infection with Bact. granulosis. The use of the Reynals' factor or the selection of monkeys whose general resistance had been lowered by a tubercular infection, by severe malnutrition, or by the injection of benzol, did not increase the virulence of old strains of Bact. granulosis. This investigation has confirmed the observations of Noguchi; Olitsky, Knutti and Tyler and Thygeson that characteristic lesions of granular conjunctivitis (“monkey trachoma”) may be initiated in rhesus monkeys by inoculating freshly isolated, virulent strains of Bact. granulosis, but more effectively by infected monkey tissue containing Bact. granulosis. The lesions thus induced at times pass spontaneously to the uninoculated eye and are transmissible in series by injection of tissue suspensions. It was not possible to demonstrate the presence of any filtrable virus or auxiliary agent in the conjunctival lesions of monkeys which were used in transmission experiments. It was demonstrated in several monkeys which showed no gross evidence of follicles after inoculation with Noguchi's bacillus, that microscopical evidence of changes indicative of a chronic inflammation may be present. These consist of lymphocytic and plasmocellular infiltration, edema of the conjunctiva with mucoid degeneration of the cylindrical cell epithelium and congestion of the capillaries. Clinical and experimental data are presented which indicate that spontaneous folliculosis of rhesus monkeys is a disease distinct from that which is produced by the inoculation of virulent cultures of Bact. granulosis.