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N Landshman

Publications and source records attributed to N Landshman.

11 recordsLinked to original sources

Effect of corticosteroids on healing of the corneal endothelium in cats.

BACKGROUND: Anterior segment surgery is frequently complicated by damage to the corneal endothelium. We examined the effects of corticosteroids, which are widely used for the suppression of postoperative inflammation, on the process of endothelial cell regeneration. METHODS: The effect of corticosteroids on healing of the corneal endothelium was examined in 10 domestic cats. In both eyes a circular area, 8 mm in diameter, was scraped off at the center of the corneal endothelium without damaging Descemet's membrane. Immediately after scraping, as well as 2 and 5 days later, each animal received a unilateral retrobulbar injection of betamethasone sodium phosphate (2 mg). The other eye served as a control and received a retrobulbar injection of the vehicle only. RESULTS: Evaluation of the corneal endothelium 2, 5 and 7 days after the trauma revealed that relative to the control contralateral eyes, the corticosteroid-treated eyes exhibited a higher mean coefficient of variation of the corneal endothelium cell area, fewer hexagonal cells, a larger number of polygonal cells with 3, 4 7 and 8 cellular facets, thinner corneas and less inflammation. CONCLUSIONS: These findings suggest that corticosteroids unfavorably affect the regeneration of corneal endothelial cells after injury. As corticosteroids appear to have both positive and adverse effects on corneal function after trauma, they should be used with caution.

Animals↗

Cell division in the healing of the corneal endothelium of cats.

The pattern of cell division of the corneal endothelium of cats was studied during the first week following scraping of 35.2% to 38.3% of the endothelial cells. A small number of mitoses were found 2 days after scraping (mean +/- SD, 8.2 +/- 6.1 per cornea); the number peaked during the third and the fourth days (148.5 +/- 74.5 and 206.8 +/- 40.1, respectively), sharply decreased on the fifth day to a level of 17.0 +/- 9.5, and further decreased on the sixth and seventh days to 4.2 +/- 1.8 and 3.3 +/- 1.5 mitoses per cornea, respectively. Due essentially to amitotic cell division, a multinuclear cell population, mainly binuclear, appeared and increased to a number of 3999 +/- 746 and 3,129 +/- 877 on the sixth and seventh days, respectively, after scraping. Thus, mitotic and amitotic cell division is an integral part of the posttraumatic regeneration process of the corneal endothelium of cats.

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Relationship between morphology and functional ability of regenerated corneal endothelium.

Cat corneal endothelium was damaged by a methylmethacrylate segment introduced into the anterior chamber. Within 3 to 6 months after each such operation the endothelial cell density (ECD) diminished, ranging from 1933 to as low as 450 (78% to 16%, respectively, of its preoperative value [PV]). Decrease in the ECD to between 1050 and 1150 (40%-45% of PV) made no impact on the corneal thickness (group 1: "non-swollen" corneas); further decrease was followed by an increase of the corneal thickness to a level of 11.5%-73.5% more than its preoperative value (group 2: "swollen" corneas). The coefficient of variation of ECD increased in both groups. The number of hexagonal endothelial cells diminished, while cells with three or nine or more facets appeared. All these changes were much more pronounced and verifiable in the group 2 corneas, which were distinguished by the appearance of giant endothelial cells, 2957-4095 micron2, ie, 7.5-13.5 times larger than the cells of undamaged endothelium. These data appear to indicate that the decrease of ECD to 1050 to 1150 (40% to 45% of its PV) does not provoke decompensation of the dehydrative function of the endothelium, whereas further decrease does provoke such decompensation, the giant endothelial cells probably being the main factor in this phenomenon.

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Regeneration of cat corneal endothelium induced in vivo by fibroblast growth factor.

The corneal endothelium of man, primates and carnivores has limited regenerative ability. Fibroblast growth factor (FGF) stimulates the proliferation of various mesoderm-derived cells, including corneal endothelial cells, in vitro. In the present work the effect of FGF on the regeneration of injured cat endothelium in vivo was studied. Scraping of cat corneal endothelium off Descemet's membrane was carried out by a specially designed instrument. FGF from crude preparations (25 micrograms in 50 microliter saline) or affinity purified FGF (0.5 micrograms in 25 microliter saline) were injected immediately after the scraping of the endothelium, and in both cases significant stimulation of endothelium regeneration was observed. During the first 2 weeks after scraping, the endothelial cell density (ECD) in FGF-treated eyes was higher by a factor of 1.7-2.3 than that in the control eyes. This marked difference decreased with time, but even after 12 weeks the ECD in FGF-treated eyes was higher by a factor of 1.15-1.30 than in the control eyes. Furthermore, FGF improved the polygonal shape of the cells and decreased the corneal thickness. These results clearly demonstrate the efficacy of FGF in inducing the proliferation of cat corneal endothelial cells in vivo and indicate its potential application in clinical practice.

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Further evidence for the involvement of immunoregulatory processes in corneal alkali burns: effects of immunosuppression and convalescent serum.

Alkali burns were produced in one eye of a group of mice. Two, 3 and 4 weeks later the second eye of each mouse was similarly burned. The rate of perforation in the second-burned eyes was significantly higher than in the first eye. This effect was abolished by immunosuppressing the animals before the burning of the first eyes. This potentiation effect of an ocular burn on subsequent ones is transferable to other mice by intraperitoneal administration of convalescent serum prepared from mice that were previously burned. This evidence suggests that ocular alkali burns cause the appearance in the circulation of antigens not previously present there. The antibodies produced against these antigens exacerbate the subsequent burn lesion and perhaps also the condition of the original burn.

Alkalies↗

A model of corneal re-endotheliazation after surgical trauma.

A model for simulating the endothelial damage caused by surgery is described. The model consists of the introduction of a specially constructed instrument into the anterior chamber and using it for scraping the endothelium of a pre-determined, precisely quantifiable area of cornea. The process of healing of the scraped cornea can be followed and measured accurately by biomicroscopy, specular microscopy and histological techniques. The model can be used to study the qualitative and quantitative aspects of endothelium healing and the effects of the various endogenous, exogenous and iatrogenic factors on this process. The preliminary data presented shows that the healed endothelium consists of larger and less densly packed cells. The cell density is reduced by 43.3% after one scraping of 57% of the endothelium and by 69.2% after two such operations. Prolonged mild traumatic iritis causes the appearance of endothelial cells with incongruous shapes.

Animals↗

Indications for the role of the immune system in the pathogenesis of corneal alkali burns.

We produced alkali burns (1.5 N NaOH) in the right eyes of 63 mice. Three weeks later the left eye of each mouse was similarly burned. All eyes were followed up weekly for 4 weeks after the burn and were graded according to the severity of the lesion. The lesions developed much faster and were more severe in the left eyes. These results suggest that the body's immune mechanism participates in the pathogenesis of alkali corneal burns and adversely affects the development of this condition.

Alkalies↗

In vitro inhibition of Pseudomonas aeruginosa elastase by metal-chelating peptide derivatives.

Pseudomonas aeruginosa elastase is a zinc metalloendopeptidase, probably responsible for the tissue destruction observed during infections with this organism. The elastase of a virulent Pseudomonas aeruginosa strain (Habs serotype 1) was isolated and found to have a molecular weight of 35,000; it readily degraded elastin and cartilage proteoglycans. A series of amino acid and peptide derivatives containing the metal-chelating moieties hydroxamate, phosphoryl, or thiol were synthesized and tested as potential inhibitors of the enzyme. Inhibition constants (K(i)s) for the compounds were determined with the chromophoric substrate furylacryloyl-glycyl-l-leucyl-l-alanine. The hydroxamic acid derivatives of benzyloxycarbonyl-glycine, benzyloxycarbonyl-l-leucine and benzyloxycarbonyl-l-phenylalanine had inhibition constants in the range of 11 to 28 muM. The 2-mercaptoacetyl derivatives of l-leucyl-d-phenylalanine and l-leucyl-l-phenylalanine had K(i) values of 34 and 1.5 muM, respectively, demonstrating the stereospecificity of the inhibition. The most potent inhibitors tested were 2- mercaptoacetyl-l-phenylalanyl-l-leucine and phosphoryl-l-leucyl-l-phenylala-nine (K(i) = 0.2 muM). Similar compounds lacking the metal-chelating moiety were about 3 orders of magnitude poorer inhibitors. When the inhibition of the enzyme activity towards azocasein, elastin, or cartilage was examined, inhibitor concentrations approximately 50-fold higher than the respective K(i)s were required to obtain 60 to 90% inhibition. Virtually complete inhibition was achieved with these substrates at inhibitor concentrations 500-fold higher than the respective K(i)s (0.1 to 14 mM). Although, 2-mercaptoacetyl-l-phenylalanyl-l-leucine and phosphoryl-l-leucyl-l-phenylalanine exhibited the same affinity to the enzyme, the latter was inferior in inhibiting cartilage proteoglycan degradation. 2-Mercaptoacetyl-l-phenylalanyl-l-leucine represents a class of potent elastase inhibitors that might prove useful in the management of P. aeruginosa infections.

Cartilage↗

A method for processing paraffin sections of multilayer cultured tissue.

A simple and rapid method is described for processing histological preparations from multilayer cultures growing in plastic Petri dishes, A covering collodion film is utilized to remove the tissue from the plastic dish and transfer it onto a paper block prior to embedding in Paraplast. To avoid any disruption by the collodion of the plasticware, the cultured tissue is first immersed in a solution of collodion and absolute alcohol (1:1) and then covered with pure collodion. All steps are carried out in the cold. This procedure allows morphological, histochemical, immunofluorescent, and autoradiographic studies to be carried out on serial sections of cultured tissue.

Animals↗

Effect of estradiol on erythropoiesis and megakaryocytopoiesis in mice.

The effect of four 1.0-mg estradiol benzoate injections on hemopoiesis in the spleen and bone marrow in mice was studied. The number, concentration and mitotic activity of megakaryocytes (MKC) and number of MKC colonies in the spleen were found to be increased one and two weeks after cessation of the estradiol injections. MKC concentration in the bone marrow rose during the experimental period. The MKC increased in number during the first week after estradiol, but dropped to normal after the second week. The number and mitotic activity of erythroid precursors increased in the bone marrow and spleen three days after the cessation of estradiol injections. These findings suggest that estrogen enhances megakaryocytopoiesis and erythropoiesis in the bone marrow and spleen in mice.

Animals↗

Lid suture myopia in developing chicks: optical and structural considerations.

In a group of chickens studied after lid suture in the first month post hatching an unusually high myopia was found (n = 8 eyes; average: -21.87 Diopters). The non-operated eyes of these chicks had the same optical properties (n = 4; +0.93 Diopters) as the eyes of the normal control chicks (n = 12; +0.81 Diopters). Although enlargement of the whole eye occurred, the main determinant was an axial elongation (operated eyes, 18.0 mm; nonoperated, 13.7 mm; normal controls, 14.7 mm). The axial change involves an enlargement of the posterior as well as the anterior segments of the eye. Despite several structural characteristics specific to chicks, their eyes can serve as a model for myopia research.

Animals↗