RESUMEN
Inflammation of the corneal stroma (stromal keratitis) is a serious complication of infection with the nematode parasite Onchocerca volvulus. Because stromal keratitis is believed to be immunologically mediated in humans, we used a murine model to examine the role of T cells and T helper cell cytokines in the immunopathogenesis of these eye lesions. BALB/c mice immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens (OvAg) developed pronounced corneal opacification and neovascularization. The corneal stroma was edematous and contained numerous eosinophils and mononuclear cells. Stromal keratitis in immunized mice was determined to be T cell dependent based on the following observations: (a) T cell-deficient nude mice immunized and injected intrastromally with OvAg fail to develop corneal pathology; and (b) adoptive transfer of spleen cells from OvAg-immunized BALB/c mice to naive nude mice before intrastromal injection of OvAg results in development of keratitis. OvAg-stimulated lymph node and spleen cell cytokine production was dependent on CD4 cells and included interleukin (IL)-4 and IL-5, but not interferon gamma, indicating a predominant T helper type 2 cell-like response. Inflamed corneas from immunized BALB/c mice and from reconstituted nude mice had greatly elevated CD4 and IL-4 gene expression compared with interferon gamma. Mice in which the IL-4 gene was disrupted failed to develop corneal disease, demonstrating that IL-4 is essential in the immunopathogenesis of O. volvulus-mediated stromal keratitis.
Asunto(s)
Interleucina-4/metabolismo , Queratitis/inmunología , Oncocercosis Ocular/inmunología , Células Th2/inmunología , Animales , Antígenos Helmínticos/inmunología , Secuencia de Bases , Córnea/irrigación sanguínea , Córnea/patología , Opacidad de la Córnea , Femenino , Inmunoterapia Adoptiva , Interleucina-4/deficiencia , Interleucina-4/genética , Queratitis/inducido químicamente , Queratitis/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Datos de Secuencia Molecular , Neovascularización Patológica/patología , Oncocercosis Ocular/patologíaRESUMEN
Lumican, a prototypic leucine-rich proteoglycan with keratan sulfate side chains, is a major component of the cornea, dermal, and muscle connective tissues. Mice homozygous for a null mutation in lumican display skin laxity and fragility resembling certain types of Ehlers-Danlos syndrome. In addition, the mutant mice develop bilateral corneal opacification. The underlying connective tissue defect in the homozygous mutants is deregulated growth of collagen fibrils with a significant proportion of abnormally thick collagen fibrils in the skin and cornea as indicated by transmission electron microscopy. A highly organized and regularly spaced collagen fibril matrix typical of the normal cornea is also missing in these mutant mice. This study establishes a crucial role for lumican in the regulation of collagen assembly into fibrils in various connective tissues. Most importantly, these results provide a definitive link between a necessity for lumican in the development of a highly organized collagenous matrix and corneal transparency.
Asunto(s)
Proteoglicanos Tipo Condroitín Sulfato/fisiología , Colágeno/metabolismo , Opacidad de la Córnea/etiología , Sulfato de Queratano/fisiología , Enfermedades Cutáneas Metabólicas/etiología , Animales , Proteoglicanos Tipo Condroitín Sulfato/genética , Opacidad de la Córnea/patología , Expresión Génica , Marcación de Gen , Hibridación in Situ , Sulfato de Queratano/genética , Lumican , Ratones , Enfermedades Cutáneas Metabólicas/patología , Resistencia a la TracciónRESUMEN
Paired human crystalline lenses (n = 21, patient ages 20-79 years) were extracted for lipids with chloroform-methanol 2:1, using the Folch method. The extracted crude lipids were analyzed at 202.4 MHz by phosphorus-31 magnetic resonance spectroscopy (31P NMR). Fourteen membrane phospholipids were detected including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylcholine plasmalogen (PC plas), phosphatidylethanolamine (PE), phosphatidylethanolamine plasmalogen, lysophosphatidylethanolamine (PA), phosphatidylglycerol (PG), lysophosphatidylglycerol, phosphatidylserine (PS), phosphatidic acid, phosphatidylinositol, sphingomyelin (SPH), and two uncharacterized phospholipids. The uncharacterized phospholipid at 0.13 was the predominant phospholipid, comprising 43.20% of the lens phospholipid profile. A decrease in mole percent of phosphorus concentrations of PE, PC plas, and PC and an increase in SPH correlated with age. The following computed indices decreased with age: PC/PG and PE/PS; PC + PE; (PC + PC plas); and PC/PS. The following computed indices increased with age: (PC + SPH)/(PE + PS), SPH/PG, (PC + SPH)/(PE + PS), LPC/PC, LPE/PE, SPH/PE, and SPH/PC. Changes in membrane phospholipids of the crystalline lens with age as detected by 31P NMR can be used to fingerprint lens maturation.
Asunto(s)
Envejecimiento/metabolismo , Cristalino/metabolismo , Fosfolípidos/metabolismo , Adulto , Humanos , Espectroscopía de Resonancia Magnética , Persona de Mediana EdadRESUMEN
Complement is present in ocular fluids, but the molecular mechanism(s) restricting its activation to exogenous targets and not to autologous ocular cells are currently unknown. To clarify how this control is achieved, monoclonal antibody (mAb)-based techniques were used to examine the eye, the lacrimal gland, and ocular fluids for the decay-accelerating factor (DAF), a membrane regulatory protein which protects blood cells from autologous complement activation on their surfaces. Immunohistochemical staining of tissue sections revealed DAF antigen on corneal and conjunctival epithelia, corneal endothelium, trabecular meshwork, and retina, as well as on lacrimal gland acinar cells and in adjacent lumens. By flow cytometry, cultures of conjunctival epithelium exhibited the highest DAF levels and levels on corneal epithelium greater than corneal endothelium greater than conjunctival fibroblasts. Biosynthetic labeling of corneal endothelium yielded de novo DAF protein with an apparent molecular weight (Mr) of 75 kD, approximating that of blood cell DAF protein, and digestions of conjunctival epithelium with phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme which cleaves glycoinositolphospholipid membrane anchors, released approximately 70% of the ocular surface DAF protein similar to leukocyte surface DAF protein. Quantitations of DAF by radioimmunometric assay employing mAbs against two DAF epitopes revealed 325 ng/ml (n = 12), 4.8 ng/ml (n = 10), and 22.0 ng/ml (n = 8) of soluble DAF antigen in tears, aqueous humor, and vitreous humor, respectively. Western blot analyses of the tear DAF antigen revealed two DAF forms, one with an apparent Mr of 72 kD resembling membrane DAF forms in other sites, and a second with an apparent Mr of 100 kD, which is previously undescribed. Since DAF activity is essential physiologically in protecting blood cells from autologous complement attack, the identification of DAF on the ocular surface, intraocularly, in the lacrimal gland, and in tears suggests that DAF-mediated control of complement activation is also required in these locations.
Asunto(s)
Ojo/análisis , Aparato Lagrimal/análisis , Proteínas de la Membrana/análisis , Anticuerpos Monoclonales , Antígenos de Superficie/análisis , Antígenos de Superficie/biosíntesis , Humor Acuoso/análisis , Western Blotting , Antígenos CD55 , Células Cultivadas , Activación de Complemento , Conjuntiva/análisis , Córnea/análisis , Epitelio/análisis , Citometría de Flujo , Humanos , Inmunohistoquímica , Ensayo Inmunorradiométrico , Proteínas de la Membrana/biosíntesis , Conformación Molecular , Lágrimas/análisisRESUMEN
PURPOSE: Gene targeted lumican-null mutants (lum(tm1sc)/lum(tm1sc)) have cloudy corneas with abnormally thick collagen fibrils. The purpose of the present study was to analyze the loss of transparency quantitatively and to define the associated corneal collagen fibril and stromal defects. METHODS: Backscattering of light, a function of corneal haze and opacification, was determined regionally using in vivo confocal microscopy in lumican-deficient and wild-type control mice. Fibril organization and structure were analyzed using transmission electron microscopy. Biochemical approaches were used to quantify glycosaminoglycan contents. Lumican distribution in the cornea was elucidated immunohistochemically. RESULTS; Compared with control stromas, lumican-deficient stromas displayed a threefold increase in backscattered light with maximal increase confined to the posterior stroma. Confocal microscopy through-focusing (CMTF) measurement profiles also indicated a 40% reduction in stromal thickness in the lumican-null mice. Transmission electron microscopy indicated significant collagen fibril abnormalities in the posterior stroma, with the anterior stroma remaining relatively unremarkable. The lumican-deficient posterior stroma displayed a pronounced increase in fibril diameter, large fibril aggregates, altered fibril packing, and poor lamellar organization. Immunostaining of wild-type corneas demonstrated high concentrations of lumican in the posterior stroma. Biochemical assessment of keratan sulfate (KS) content of whole eyes revealed a 25% reduction in KS content in the lumican-deficient mice. CONCLUSIONS: The structural defects and maximum backscattering of light clearly localized to the posterior stroma of lumican-deficient mice. In normal mice, an enrichment of lumican was observed in the posterior stroma compared with that in the anterior stroma. Taken together, these observations indicate a key role for lumican in the posterior stroma in maintaining normal fibril architecture, most likely by regulating fibril assembly and maintaining optimal KS content required for transparency.
Asunto(s)
Proteoglicanos Tipo Condroitín Sulfato/deficiencia , Colágeno/ultraestructura , Opacidad de la Córnea/patología , Sustancia Propia/ultraestructura , Sulfato de Queratano/deficiencia , Animales , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Colágeno/metabolismo , Opacidad de la Córnea/metabolismo , Sustancia Propia/metabolismo , Marcación de Gen , Sulfato de Queratano/metabolismo , Lumican , Ratones , Ratones Noqueados , Microscopía Confocal , Microscopía FluorescenteRESUMEN
PURPOSE: Intrastromal injection of mice with antigens from the parasitic helminth that causes river blindness (Onchocerca volvulus) induces eosinophil recruitment to the corneal stroma at the time of maximum corneal opacification and neovascularization. The present study was conducted to examine the role of eosinophils and neutrophils in onchocercal keratitis in control C57Bl/6 mice and in interleukin-5 gene knockout (IL-5(-/-)) mice. METHODS: C57Bl/6 and IL-5(-/-) mice were immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens. Mice were killed at various times thereafter. Development of keratitis was assessed by slit lamp examination, and inflammatory cells in the cornea were identified by immunohistochemistry. RESULTS: A biphasic recruitment of inflammatory cells was observed in C57Bl/6 mice; neutrophils predominated during the first 72 hours after intrastromal injection and subsequently declined, whereas eosinophil recruitment increased as time elapsed and comprised the majority (90%) of cells in the cornea by day 7. In contrast, neutrophils were the predominant inflammatory cells in IL-5(-/-) mice at early and late time points and were associated with extensive stromal damage and corneal opacification and neovascularization. Eosinophils were not detected in these mice at any time. CONCLUSIONS: In the absence of eosinophils, neutrophils can mediate keratitis induced by helminth antigens. Together with the early neutrophilic infiltrate in control animals, these observations indicate that neutrophils have an important role in onchocercal keratitis.
Asunto(s)
Eosinófilos/fisiología , Queratitis/inmunología , Neutrófilos/fisiología , Onchocerca volvulus/inmunología , Oncocercosis Ocular/inmunología , Animales , Antígenos Helmínticos/administración & dosificación , Córnea/inmunología , Córnea/parasitología , Córnea/patología , Neovascularización de la Córnea/inmunología , Neovascularización de la Córnea/parasitología , Neovascularización de la Córnea/patología , Opacidad de la Córnea/inmunología , Opacidad de la Córnea/parasitología , Opacidad de la Córnea/patología , Citocinas/metabolismo , Cartilla de ADN/química , Femenino , Técnicas para Inmunoenzimas , Interleucina-5/genética , Interleucina-5/metabolismo , Queratitis/parasitología , Queratitis/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oncocercosis Ocular/metabolismo , Oncocercosis Ocular/patología , Bazo/metabolismoRESUMEN
PURPOSE: A murine model of helminth-induced keratitis (river blindness) that is characterized by a biphasic recruitment of neutrophils (days 1-3) and eosinophils (days 3+) to the cornea has been developed. The purpose of this study was to determine the relative contribution of P- and E-selectin in recruitment of these inflammatory cells from limbal vessels to the corneal stroma. METHODS: P- and E-selectin gene knockout (-/-) mice were immunized with antigens extracted from the parasitic helminth Onchocerca volvulus. One week after the last immunization, parasite antigens were injected directly into the corneal stroma. Mice were killed on days 1 and 3 postchallenge, and eyes were immunostained with either anti-eosinophil major basic protein (MBP) or with anti-neutrophil Ab. The number of cells in the cornea was determined by direct counting. RESULTS: Recruitment of eosinophils to the cornea was significantly impaired in P-selectin(-/-) mice (63.9% fewer eosinophils on day 1 [P: = 0.0015], and 61% fewer on day 3 [P: < 0.0001]) compared with control C57BL/6 mice. In contrast, P-selectin deficiency had no effect on neutrophil recruitment to the cornea. There was no inhibition of eosinophil and neutrophil migration to the corneas of E-selectin(-/-) mice, indicating that there is no direct role for this adhesion molecule in helminth-induced keratitis. CONCLUSIONS: The present study demonstrates that P-selectin is an important mediator of eosinophil recruitment to the cornea. P-selectin interactions may therefore be potential targets for immunotherapy in eosinophil-mediated ocular inflammation.
Asunto(s)
Quimiotaxis de Leucocito/inmunología , Córnea/inmunología , Eosinófilos/inmunología , Queratitis/inmunología , Onchocerca volvulus/inmunología , Oncocercosis Ocular/inmunología , Selectina-P/fisiología , Ribonucleasas , Animales , Antígenos Helmínticos/inmunología , Proteínas Sanguíneas/inmunología , Córnea/parasitología , Córnea/patología , Modelos Animales de Enfermedad , Selectina E/genética , Selectina E/fisiología , Ensayo de Inmunoadsorción Enzimática , Proteínas en los Gránulos del Eosinófilo , Técnica del Anticuerpo Fluorescente Indirecta , Inmunización , Técnicas para Inmunoenzimas , Inmunoglobulina E/análisis , Interleucina-5/metabolismo , Queratitis/parasitología , Queratitis/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/inmunología , Oncocercosis Ocular/parasitología , Oncocercosis Ocular/patología , Selectina-P/genética , Bazo/citología , Bazo/metabolismoRESUMEN
PURPOSE: The authors investigated whether healing of cat corneal endothelial wounds could be enhanced in vivo by human epidermal growth factor (EGF). METHODS: EGF was administered in sodium hyaluronate to the anterior chamber of cats after an endothelial touch injury. Control contralateral eyes received sodium hyaluronate alone. At selected times after injury, the corneas were evaluated for thickness, the rate of endothelial wound closure, the endothelial cell density, any variation in cell size, the percentage of hexagonal cells, and endothelial cell mitosis. RESULTS: Two days after injury, endothelial wounds of eyes treated with EGF had healed an average of 65 +/- 4% of the initial 38.5 mm2 wound area; paired control eyes had healed an average of 59 +/- 4% (P < 0.05). Both EGF-treated and control wounds had resurfaced over 90% of the initial wound area on day 4 after injury, and the wounds were completely resurfaced by 7 and 14 days after injury in both treatment groups. On days 4 and 7 after injury, the EGF-treated corneas were 5% and 8% thicker (835 versus 796 microns and 786 versus 728 microns, respectively) than the paired control corneas (P < 0.03). On days 10 and 14 after injury, both EGF-treated and control corneas were 19% and 12% thicker, respectively, than prewound the corneal thickness (621 microns). Seven days after injury, the corneas treated with EGF had an average of 76 +/- 28% more (P < 0.05) endothelial cell nuclei labeled with tritiated thymidine compared with that of the paired control eyes (2472 versus 1543 labeled nuclei). Fourteen days after injury, the central endothelial cell density of EGF-treated corneas was an average of 38 +/- 11% higher than that of the paired control eyes (P < 0.01, 1708 versus 1235 cells/mm2). The percentage of hexagonal cells in the wound area was an average of 14 +/- 4% higher (P < 0.01) than that of the paired control eyes (82% versus 69%), and the coefficient of variation of the cell size for EGF-treated corneas was an average of 31% (P < 0.05) smaller than that of the paired control corneas (0.21 versus 0.29 [standard deviation]/mean cell size). CONCLUSIONS: A single intraocular application of EGF formulated in sodium hyaluronate after an endothelial cell injury significantly enhanced multiple parameters that are closely related to improved endothelial cell regeneration.
Asunto(s)
Endotelio Corneal/efectos de los fármacos , Factor de Crecimiento Epidérmico/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Gatos , Recuento de Células , Córnea/efectos de los fármacos , Córnea/patología , Replicación del ADN , Modelos Animales de Enfermedad , Endotelio Corneal/lesiones , Endotelio Corneal/patología , Femenino , Ácido Hialurónico/administración & dosificación , Masculino , Mitosis/efectos de los fármacos , Distribución Aleatoria , Proteínas Recombinantes/farmacologíaRESUMEN
Masked controlled rabbit studies were done to determine the toxic effects on corneal wound healing of the antiviral ointments 0.5% idoxuridine, 3% Ara A, and 3% acyclovir, and the antiviral drops 0.1% idoxuridine, 3% Ara AMP, and 1% trifluridine. Ara A, acyclovir, trifluridine and idoxuridine drops had no significant effects on the rate of closure of epithelial wounds. Idoxuridine ointment given 5 times a day significantly retarded the rate of epithelial wound closure, but not when given 4 times a day. Only Ara AMP caused a retardation of epithelial healing and an actual increase in the defect after 4 days of treatment. Histopathologically all drugs, except acyclovir, showed a toxic effect on the regenerating epithelium. All drugs, except acyclovir, showed retarded stromal wound healing with reduced bursting strength and collagen content. Ara AMP had increased bursting strength and collagen content possibly because of greater inflammation. Acyclovir, in comparison to all the other medications studied, appeared to have minimal to no toxic effects on experimental epithelial and stromal wound healing, and on this basis is the agent of choice for use in herpes simplex stromal keratitis with ulceration and as a prophylactic agent for long-term use after penetrating keratoplasty.
Asunto(s)
Antivirales/toxicidad , Córnea/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Antivirales/metabolismo , Córnea/fisiología , Epitelio/efectos de los fármacos , Queratitis Dendrítica/tratamiento farmacológico , Masculino , Conejos , Regeneración/efectos de los fármacosRESUMEN
Using an in vitro system we measured the corneal epithelial cytotoxicity and the antiviral activity of the antiviral agents idoxuridine (IDU), trifluridine (TFT), ethyldeoxyuridine (EDU), and (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU). Confluent rabbit corneal epithelial cell cultures were established, and the antiviral agents were added for 5, 30, or 60 min at a range of concentrations including that used clinically (IDU 0.1%, TFT 1.0%, BVDU 0.1%, EDU 2.0%). Twelve hour [3H]thymidine incorporation then was measured and expressed as % inhibition of control cultures. In separate experiments confluent corneal epithelial cell monolayers were inoculated with 10(4) plaque forming units (PFU) of HSV type 1 (McKrae strain) for 1 h, and IDU 0.1%, TFT 1.0%, and BVDU 0.1% were added to the culture for determination of PFU inhibition. Significant dose-, but not time-dependent, toxicity was observed at the clinical concentrations of IDU, TFT, and EDU. Toxicity was absent for BVDU. TFT and IDU were the most toxic, and EDU was of intermediate toxicity. IDU, TFT, and BVDU showed significant antiviral activity in this corneal epithelial cell culture system (TFT greater than BVDU greater than IDU). The results of this in vitro study paralleled the findings of previous in vivo corneal epithelial toxicity studies of IDU, TFT, and BVDU. Our data, however, suggest that EDU has a potential for clinical toxicity and further studies are recommended. Our model may be useful in the future toxicologic study of new antiviral agents.
Asunto(s)
Antivirales/toxicidad , Córnea/efectos de los fármacos , Animales , Bromodesoxiuridina/análogos & derivados , Bromodesoxiuridina/toxicidad , Supervivencia Celular/efectos de los fármacos , Córnea/metabolismo , Desoxiuridina/análogos & derivados , Desoxiuridina/toxicidad , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Idoxuridina/toxicidad , Técnicas In Vitro , Conejos , Timidina/metabolismo , Trifluridina/toxicidadRESUMEN
The concentrations of corneal phosphatic metabolites in fresh and eye-bank-processed corneas were measured by phosphorus 31 nuclear magnetic resonance of perchloric acid corneal extracts to determine whether metabolic differences exist between these two corneal preparations. Cat corneas were prepared using an eye-bank protocol, including specular microscopic examination and transport to a distant location. Fresh cat corneas were used as controls. The hexose 6-phosphate resonance band, the nucleoside monophosphate band, the phosphodiesters, and adenosine triphosphate of eye-bank-processed corneas were significantly decreased relative to fresh control corneas. Phosphatic metabolites that significantly increased relative to control corneas included inorganic orthophosphate and phosphocreatine. A calculated corneal tissue-energy index was significantly decreased for eye-bank-processed corneas relative to control. This decline demonstrates a compromise in the metabolic energy status of the tissue and is indicative of a diminished ability of the cornea to maintain its complement of high-energy phosphates.
Asunto(s)
Córnea/metabolismo , Compuestos Organofosforados/análisis , Conservación de Tejido , Adenosina Trifosfato/análisis , Animales , Gatos , Metabolismo Energético , Bancos de Ojos , Espectroscopía de Resonancia Magnética , Isótopos de FósforoRESUMEN
Application of nondestructive and noninvasive nuclear magnetic resonance (NMR) techniques to the evaluation of corneal donor tissue metabolism may provide information that would allow improved selection of donor material for keratoplasty. A phosphorus 31 NMR spectrum was generated from a single intact human cornea, evaluating phosphatic metabolites qualitatively and quantitatively. The NMR analyses were conducted on four corneas (from patients aged from 73 to 75 years). Intracorneal pH (7.2) was monitored from the resonance shift position of inorganic orthophosphate (Pi). A numerical index (1.15) of tissue energy status was determined by comparing the relative tissue content of high-field, high-energy phosphate signals (adenosine triphosphate, adenosine diphosphate, nicotinamide-adenine dinucleotide, and the uridine diphospho-hexoses) to that of the low-field, low-energy phosphate signals (Pi, sugar phosphates, and phosphodiesters). This is the first demonstration of the feasibility of using nondestructive 31P NMR to monitor the metabolic status of a single intact eye bank cornea as would be required in the evaluation of eye bank tissue before keratoplastic procedures.
Asunto(s)
Córnea/análisis , Bancos de Ojos , Espectroscopía de Resonancia Magnética , Bancos de Tejidos , Supervivencia Tisular , Adenosina Difosfato/análisis , Adenosina Trifosfato/análisis , Anciano , Glicerilfosforilcolina/análisis , Humanos , NAD/análisis , NADP/análisis , Fosfatos de Azúcar/análisis , Uridina Difosfato Galactosa/análisis , Uridina Difosfato Glucosa/análisis , Azúcares de Uridina Difosfato/análisisRESUMEN
We studied, in a rabbit, the ocular toxicity of topical 1% solutions or suspensions of amphotericin B, flucytosine, miconazole nitrate, and ketoconazole. Flucytosine, miconazole, and ketoconazole did not retard the closure of 8.5-mm corneal epithelial defects; amphotericin B greatly retarded the closure of such defects. Amphotericin B produced dramatic pathologic changes in this model; these changes worsened with each day of therapy. Ketoconazole produced modest biomicroscopically and histologically detectable pathologic changes in the regenerating corneal epithelium; flucytosine and miconazole did not produce such changes.
Asunto(s)
Antifúngicos/efectos adversos , Ojo/efectos de los fármacos , Administración Tópica , Anfotericina B/efectos adversos , Animales , Córnea/efectos de los fármacos , Flucitosina/efectos adversos , Imidazoles/efectos adversos , Iritis/inducido químicamente , Cetoconazol , Miconazol/efectos adversos , Piperazinas/efectos adversos , ConejosRESUMEN
This study report the therapeutic efficacy of systemic antiviral drugs in reducing the incidence of trigeminal ganglionic latent herpes simplex virus (HSV) after ocular infection in mice. Aciclovir sodium, 60 mg/kg daily for five days starting three and 24 hours after inoculation, resulted in a significant decrease in recovery of latent HSV, 28% and 54% positive, respectively, in comparison to untreated controls, 100% positive. Initiation of similar therapy three weeks after inoculation for 5, 10, and 15 days resulted in progressive decrease in persistence of latent virus, being 100%, 33%, and 12% positive, respectively. Systemic vidarabine, 50 mg/kg daily for 15 days starting three weeks after inoculation, also resulted in a significant decrease of positive ganglionic cultures (60% positive) in comparison to the untreated controls. The results indicate that replication of HSV in the trigeminal ganglia in mice is probably continuous and that this reservoir of recurrent ocular herpes is amenable to therapy with systemic antiviral agents.
Asunto(s)
Antivirales/uso terapéutico , Ganglios/microbiología , Guanina/análogos & derivados , Queratitis Dendrítica/tratamiento farmacológico , Nervio Trigémino/microbiología , Vidarabina/uso terapéutico , Animales , Antivirales/farmacología , Ganglios/efectos de los fármacos , Guanina/farmacología , Guanina/uso terapéutico , Masculino , Ratones , Simplexvirus/efectos de los fármacos , Simplexvirus/aislamiento & purificación , Nervio Trigémino/efectos de los fármacos , Vidarabina/farmacologíaRESUMEN
Four patients had idoxuridine-induced conjunctival cicatrization similar to ocular cicatricial pemphigoid develop, but in the treated eye only. Three of the four patients had chronic, recurrent herpes simplex epithelial and stromal keratitis. The fourth patient had Sjögren's syndrome. All received idoxuridine (0.1% drops and/or 0.5% ointment) and topical corticosteroids from one to 3 1/2 years. Substantial morbidity resulted that included visual loss, stromal ulceration, corneal scarring, and keratinization. Conjunctival biopsy specimens showed cicatrization with a mixed inflammatory cell reaction and absence of goblet cells. Results of direct immunofluorescent microscopy of the conjunctiva were either negative or nonspecific for autoantibody. No circulating autoantibody was detected in any of the four patients.
Asunto(s)
Enfermedades de la Conjuntiva/inducido químicamente , Idoxuridina/efectos adversos , Penfigoide Benigno de la Membrana Mucosa/inducido químicamente , Enfermedades Cutáneas Vesiculoampollosas/inducido químicamente , Enfermedades de la Conjuntiva/patología , Enfermedades de la Conjuntiva/terapia , Femenino , Humanos , Queratitis Dendrítica/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Penfigoide Benigno de la Membrana Mucosa/patología , Penfigoide Benigno de la Membrana Mucosa/terapia , Síndrome de Sjögren/tratamiento farmacológicoRESUMEN
To elucidate the pathogenic mechanisms involved in onchocercal sclerosing keratitis in humans, we developed a model of onchocercal interstitial keratitis in guinea pigs. Onchocerca volvulus antigens injected intrastromally into corneas of preimmunized Hartley guinea pigs induced an intense stromal keratitis with corneal edema, neovascularization, and infiltration with acute and chronic inflammatory cells. This reaction subsided after two weeks. Repeated intrastromal injection resulted in an exacerbation of the keratitis and ultimately in residual scarring. These findings are consistent clinically and histopathologically with the chronic interstitial keratitis observed in humans. To define which antigens induce the corneal reaction, O volvulus antigens were separated by molecular sieve chromatography and injected intrastromally. The highest activity was shown to reside in the fraction containing molecules of intermediate molecular weight. This model will be useful in defining O volvulus antigens and their role in sclerosing keratitis as well as in elucidating the immune mechanisms involved.
Asunto(s)
Antígenos Helmínticos/inmunología , Queratitis/parasitología , Onchocerca/inmunología , Animales , Antígenos Helmínticos/administración & dosificación , Antígenos Helmínticos/análisis , Sustancia Propia/irrigación sanguínea , Sustancia Propia/patología , Edema/patología , Femenino , Adyuvante de Freund/administración & dosificación , Cobayas , Inmunización , Inyecciones , Queratitis/inmunología , Neovascularización Patológica/patologíaRESUMEN
Thirty-three epikeratoplasties were performed on 31 keratoconic contact lens intolerant patients. Thirty-two of these procedures were anatomically successful with clear lenticules and flattening of the postoperative keratometric measurements in all but one eye. One patient's lenticule developed a persistent epithelial defect that eventually required its removal at 42 days. This patient subsequently underwent a successful penetrating keratoplasty. Of the 32 eyes that were anatomically successful, 20 eyes in 19 patients were able to achieve satisfactory visual improvement requiring either no correction or spectacle lenses. Twelve eyes in 11 patients were successfully refit with contact lenses for anisometropic refractive errors (11 eyes) and residual irregular astigmatism (one eye). Three patients (two in the non-contact lens group and one in the contact lens group) have subsequently undergone penetrating keratoplasty for further visual improvement. Our data suggest that the majority of keratoconic epikeratoplasties achieve a satisfactory visual result either unaided or with spectacles; however, those patients who wish to resume contact lens wear may do so successfully.
Asunto(s)
Lentes de Contacto , Trasplante de Córnea , Queratocono/cirugía , Adulto , Anteojos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Errores de Refracción/etiología , Factores de Tiempo , Agudeza VisualRESUMEN
The effect of medroxyprogesterone acetate treatment in preventing or retarding corneal ulceration after alkali burns was studied in rabbits in an attempt to correlate dose and response. The eyes were treated for 21 days with a 0.01% or 1% suspension administered topically four times a day or medroxyprogesterone acetate, 4 mg or 30 mg, given subconjunctivally on alternate days. None of these regimens was noticeably effective, although at times there was a trend toward retarding ulceration. Thus, it was not possible to confirm earlier reports of substantial efficacy of medroxyprogesterone. Corneal stroma with epithelial defects and/or ulcers persistently showed infiltration with neutrophils in the superficial stroma within the epithelial defect, implicating the tears as the source of the inflammatory cells.
Asunto(s)
Quemaduras Químicas/tratamiento farmacológico , Úlcera de la Córnea/tratamiento farmacológico , Quemaduras Oculares/inducido químicamente , Medroxiprogesterona/uso terapéutico , Álcalis , Animales , Quemaduras Químicas/complicaciones , Úlcera de la Córnea/etiología , Modelos Animales de Enfermedad , Quemaduras Oculares/complicaciones , ConejosRESUMEN
The clinical records and serial corneal endothelial images of 25 acapsular, pseudophakic eyes with Kelman-style, one-piece, anterior-chamber intraocular lenses and 24 acapsular, pseudophakic eyes with suture-fixated, posterior-chamber intraocular lenses following penetrating keratoplasty were reviewed to determine clinical success and endothelial survival after 1 year. Twenty-two (88%) of 25 grafts in the anterior-chamber intraocular lens group and 23 (96%) of 24 grafts in the sutured posterior-chamber intraocular lens group were clear after 1 year; best corrected visual acuity of 20/40 or better was noted in 25% of the eyes in the anterior-chamber intraocular lens group and 29% of the eyes in the sutured posterior-chamber intraocular lens group. The mean intraocular pressure for the anterior-chamber intraocular lens group was significantly lower than for the sutured posterior-chamber intraocular lens group at 3 months (17 +/- 4 vs 21 +/- 7 mm Hg) and at 6 months (17 +/- 3 vs 20 +/- 5 mm Hg); but did not differ at 1 year. The mean percent of endothelial cell loss after 1 year did not differ between the anterior-chamber intraocular lens group (32% +/- 26%) and the sutured posterior-chamber intraocular lens group (27% +/- 26%). No clinical or endothelial morphometric advantages were noted after 1 year for the suture-fixated, posterior-chamber intraocular lens over the Kelman-style, one-piece anterior chamber, intraocular lens following pseudophakic penetrating keratoplasty; however, a long-term, prospective, randomized study of these two intraocular lens types is recommended.
Asunto(s)
Endotelio Corneal/citología , Queratoplastia Penetrante , Lentes Intraoculares , Técnicas de Sutura , Anciano , Cámara Anterior/cirugía , Afaquia Poscatarata/cirugía , Recuento de Células , Femenino , Humanos , Presión Intraocular , Masculino , Pronóstico , Estudios Retrospectivos , Donantes de Tejidos , Agudeza VisualRESUMEN
A model of herpes simplex interstitial keratitis was developed in rabbits sensitized with live herpes simplex virus (HSV) type 2 and challenged intrastromally with live virus. This model was used to evaluate the effects of subconjunctival medroxyprogesterone acetate on the course of the disease and on collagenase levels in the treated corneas. Whether treated prophylactically or therapeutically, the medroxyprogesterone-treated groups had substantially less stromal infiltration and neovascularization than the controls. The clinical effects corresponded with a marked reduction in the polymorphonuclear leukocyte infiltrate histologically, and the suppression of latent and active collagenase activity in the treated corneas cultured in vitro. However, epithelial disease was exacerbated in prophylactically treated animals. Medroxyprogesterone appears to be useful in the treatment of herpetic interstitial keratitis as an anti-inflammatory agent as well as an inhibitor of collagenase production but, like the corticosteroids, it can exacerbate epithelial disease.