RESUMEN
Congenital stationary night blindness (CSNB) is an inherited retinal disease that causes a profound loss of rod sensitivity without severe retinal degeneration. One well-studied rhodopsin point mutant, G90D-Rho, is thought to cause CSNB because of its constitutive activity in darkness causing rod desensitization. However, the nature of this constitutive activity and its precise molecular source have not been resolved for almost 30 y. In this study, we made a knock-in (KI) mouse line with a very low expression of G90D-Rho (equal in amount to ~0.1% of normal rhodopsin, WT-Rho, in WT rods), with the remaining WT-Rho replaced by REY-Rho, a mutant with a very low efficiency of activating transducin due to a charge reversal of the highly conserved ERY motif to REY. We observed two kinds of constitutive noise: one being spontaneous isomerization (R*) of G90D-Rho at a molecular rate (R* s-1) 175-fold higher than WT-Rho and the other being G90D-Rho-generated dark continuous noise comprising low-amplitude unitary events occurring at a very high molecular rate equivalent in effect to ~40,000-fold of R* s-1 from WT-Rho. Neither noise type originated from G90D-Opsin because exogenous 11-cis-retinal had no effect. Extrapolating the above observations at low (0.1%) expression of G90D-Rho to normal disease exhibited by a KI mouse model with RhoG90D/WTand RhoG90D/G90D genotypes predicts the disease condition very well quantitatively. Overall, the continuous noise from G90D-Rho therefore predominates, constituting the major equivalent background light causing rod desensitization in CSNB.
Asunto(s)
Enfermedades Hereditarias del Ojo , Enfermedades Genéticas Ligadas al Cromosoma X , Miopía , Ceguera Nocturna , Rodopsina , Animales , Ceguera Nocturna/genética , Ceguera Nocturna/metabolismo , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/metabolismo , Ratones , Rodopsina/genética , Rodopsina/metabolismo , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/metabolismo , Miopía/genética , Miopía/metabolismo , Células Fotorreceptoras Retinianas Bastones/metabolismo , Células Fotorreceptoras Retinianas Bastones/patología , Oscuridad , Transducina/genética , Transducina/metabolismo , Técnicas de Sustitución del Gen , Modelos Animales de EnfermedadRESUMEN
OBJETIVO: Comparar la eficacia de 3 modalidades de tratamiento en pacientes con blefaritis crónica. METODOLOGÍA: Se realizó un estudio experimental, aleatorizado y controlado en 45 pacientes (sexo femenino: 67%; edad media: 40,5 años) con diagnóstico de blefaritis crónica para comparar la eficacia de 3 modalidades de tratamiento. Grupo 1: higiene palpebral con champú neutro 3 veces/día; grupo 2: higiene palpebral con champú neutro y gel tópico de metronidazol al 0,75% 2 veces/día; grupo 3: higiene palpebral con champú neutro y pomada antibiótica de neomicina al 3,5% y polimixina al 10% con dexametasona al 0,5% 3 veces/día. Los síntomas y signos fueron valorados asignándoles puntuaciones entre 0: sin síntomas ni signos; 1: síntomas o signos leves; 2: síntomas o signos moderados y 3: síntomas o signos severos. RESULTADOS: En los 3 grupos de tratamiento se observó mejora significativa de los signos y síntomas. Mientras que los grupos 1 y 2 presentaron una mayor mejoría en todas las variables estudiadas (p < 0,05), el grupo 3 no presentó mejoría clínica para comezón (p = 0,16), ojo seco (p = 0,29), caída de pestañas (p = 0,16) ni eritema en el borde palpebral (p = 0,29). CONCLUSIÓN: La higiene palpebral con champú neutro y el uso combinado de champú neutro con gel de metronidazol reportaron mejores resultados que la higiene palpebral con champú neutro y pomada antibiótica de neomicina y polimixina con dexametasona
OBJECTIVE: To compare the efficacy of 3 treatment options in patients with chronic blepharitis. METHODOLOGY: An experimental, randomized, controlled study was conducted on 45 patients (female 67%; Mean age: 40.5 years) diagnosed with chronic blepharitis, in order to compare the effectiveness of three treatment options. Group 1: eyelid hygiene with neutral shampoo three times/day; group 2: neutral shampoo eyelid hygiene plus topical metronidazole gel 0.75% twice/day; group 3: neutral eyelid hygiene with shampoo plus neomycin 3.5% and polymyxin 10% antibiotic ointment with 0.5% dexamethasone 3 times/day. The symptoms and signs were assessed by assigning scores from 0: no symptoms and/or signs; 1: mild symptoms and/or signs, 2: moderate symptoms and/or signs; and 3: severe symptoms and/or signs. RESULTS: A significant improvement was observed in the signs and symptoms in all 3 treatment groups. While groups 1 and 2 had more improvement in all variables studied (P < .05), Group 3 showed no clinical improvement for itching (P = .16), dry eye (P = .29), eyelashes falling (P=.16), and erythema at the eyelid margin (P = .29). CONCLUSIONS: Shampoo eyelid hygiene neutral and neutral shampoo combined with the use of metronidazole gel reported better hygiene results than neutral shampoo lid with antibiotic ointment and neomycin and polymyxin dexamethasone