RESUMEN
Purpose: Radiation therapy results in severe chronic keratopathy and dry eye disease. We developed a novel mouse model for radiation keratopathy to allow future mechanistic studies. Methods: Six to 8-week-old BALB/c mice underwent sublethal irradiation to the head only from a Cesium-137 irradiator, 2 × 550 rad, 3-hours apart. Irradiated mice were clinically evaluated by corneal fluorescein staining (CFS) at 1, 2, and 3 months, after which corneas were excised and immunofluorescence histochemistry performed with anti-CD45, anti-MHC class II, and anti-ß-tubulin antibodies. Results: The survival rate after irradiation was 100%. Mice demonstrated significant CFS and hair loss around the eyes. Corneal nerve density decreased in the central and peripheral corneas (P < 0.01) at 2 and 3 months, respectively. CD45+ immune cell densities increased in the central and peripheral corneas (P < 0.005, P < 0.001) at 2 and 3 months, respectively. MHC class II, a sign of antigen presenting cell activation, significantly increased after irradiation in the central and peripheral corneas at 2 and 3 months (P = 0.02). A strong inverse correlation was noted between decreased corneal nerves and increase in CD45+ cells in the central cornea at 2 (P = 0.04, r = -0.89) and 3 months (P = 0.03, r = -0.91) after irradiation. Conclusions: We present a model of radiation keratopathy and demonstrate significant nerve loss and increase in immune cell influx and activation within months. This model will enable future investigations to understand the effects of radiation therapy on the eye, and to study mechanisms of neuro-immune crosstalk in the cornea.
Asunto(s)
Córnea/efectos de la radiación , Enfermedades de la Córnea/etiología , Síndromes de Ojo Seco/etiología , Traumatismos Experimentales por Radiación/patología , Radioterapia/efectos adversos , Animales , Córnea/inervación , Angiografía con Fluoresceína , Ratones , Ratones Endogámicos BALB C , Microscopía Confocal , Nervio Oftálmico/efectos de la radiaciónRESUMEN
OBJECTIVE: To study the relationship between treatment with diode laser transscleral cyclophotocoagulation and development a neurotrophic keratitis due to the damage of the sensitive corneal innervation. METHODS: A study was conducted on 5 eyes of 5 patients who were treated with diode laser transscleral cyclophotocoagulation and soon developed neurotrophic ulcers. Personal characteristics of the patients were collected, as well as refraction and risk factors for corneal hypoesthesia, and the parameters of the laser used in the surgery. RESULTS: It was found that the 5 patients had predisposing factors of corneal hypoesthesia prior to surgery (chronic use of topical beta blockers, surgery with corneal incisions, diabetes mellitus, or corneal dystrophies); however none had developed neurotrophic keratitis until the cyclophotocoagulation was performed. It also showed that 4 of them were highly myopic, and they all were treated with high laser parameters (with an average of 2880 mW for 3s at an average surface of 275°), triggering neurotrophic ulcers between 10 and 35 days after surgery. CONCLUSION: Neurotrophic keratitis is a rare complication that can occur after diode laser transscleral cyclophotocoagulation, secondary to the damage of the long ciliary nerves. The emergence of this disorder can be triggered by the existence of previous risk factors, including high myopia, thus it is important to respect the recommended treatment parameters to prevent the development of this disorder.
Asunto(s)
Úlcera de la Córnea/etiología , Coagulación con Láser/efectos adversos , Nervio Oftálmico/lesiones , Complicaciones Posoperatorias/etiología , Traumatismos por Radiación/etiología , Adulto , Anciano , Córnea/inervación , Opacidad de la Córnea/etiología , Femenino , Glaucoma de Ángulo Abierto/cirugía , Humanos , Coagulación con Láser/instrumentación , Coagulación con Láser/métodos , Láseres de Semiconductores , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Nervio Oftálmico/efectos de la radiación , Estudios RetrospectivosRESUMEN
Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.
Asunto(s)
Cefalea/fisiopatología , Luz/efectos adversos , Dolor/fisiopatología , Fotofobia/fisiopatología , Nervio Trigémino/fisiopatología , Nervio Trigémino/efectos de la radiación , Vías Aferentes/fisiopatología , Vías Aferentes/efectos de la radiación , Anestésicos Locales/farmacología , Animales , Cefalea/etiología , Masculino , Nociceptores/efectos de la radiación , Arteria Oftálmica/inervación , Arteria Oftálmica/fisiopatología , Nervio Oftálmico/fisiopatología , Nervio Oftálmico/efectos de la radiación , Dolor/etiología , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Fotofobia/etiología , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Rombencéfalo/efectos de los fármacos , Rombencéfalo/fisiología , Núcleo Caudal del Trigémino/fisiopatología , Núcleo Caudal del Trigémino/efectos de la radiación , Ganglio del Trigémino/fisiopatología , Ganglio del Trigémino/efectos de la radiación , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Vías Visuales/efectos de los fármacos , Vías Visuales/fisiopatologíaAsunto(s)
Epilepsia/diagnóstico , Epilepsia/etiología , Nervio Oftálmico/fisiopatología , Periodicidad , Adulto , Electroencefalografía/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Nervio Oftálmico/efectos de la radiación , Estimulación Física/efectos adversos , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
Tourette syndrome (TS) is a common disorder which typically occurs during childhood or early adolescence. There is no definitive diagnostic test for TS. The objective of this study was to demonstrate whether neurophysiological abnormalities of the blink reflex can be observed in children with TS. We enrolled 15 children with TS, diagnosed according to DSM IV Diagnostic Criteria, and 15 controls. The blink reflex was elicited by stimulating the supraorbital nerve in order to measure the early response (R1), homolateral and contralateral R2 (late) responses, amplitude of R1 and duration of R2. The mean duration of R2 was significantly longer in TS patients than in the controls (P < 0.001, Student's t-test). An abnormal pattern of the blink reflex can be, even in childhood, an early neurophysiologic marker of TS, which is not related to the duration of TS or to the age of onset.