RESUMEN
Purpose: There is an unclear relationship between ocular blood flow (OBF) and the structural characteristics of the optic nerve head (ONH) in glaucoma, a multifactorial disease. This study used laser speckle flowgraphy (LSFG) to identify low-OBF glaucoma patients and investigated the ONH in these patients. Materials and Methods: In 533 eyes with glaucoma, we determined confounding factors for LSFG-measured OBF (tissue-area mean blur rate: MT) and corrected MT with a linear mixed-effects model (LMM). Structural ONH data (from fundus stereo photography), OCT data, and clinical characteristics were then compared in patients with corrected MT in the upper and lower quartiles using the LMM. Results: Single regression showed significant correlations between MT and age, spherical equivalent (SE), central corneal thickness (CCT), and a weighted count of retinal ganglion cells (wRGC), but not axial length or systemic blood pressure. Gender also significantly influenced MT; MT was corrected for these correlated factors and also glaucoma type with the LMM. The lower-quartile MT group had a significantly larger cup area and cup-disc area ratio and lower temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and macular ganglion cell complex (GCC) than the upper-quartile group. Conclusions: Low-OBF glaucoma patients were characterized by a larger cup-disc ratio, and higher susceptibility to damage in the temporal disc and the macular area.
Asunto(s)
Glaucoma de Ángulo Abierto/fisiopatología , Disco Óptico/irrigación sanguínea , Enfermedades del Nervio Óptico/fisiopatología , Flujo Sanguíneo Regional/fisiología , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Angiografía con Fluoresceína , Glaucoma de Ángulo Abierto/diagnóstico , Hemodinámica , Humanos , Presión Intraocular/fisiología , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/diagnóstico , Células Ganglionares de la Retina/patología , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
Folding experiments have suggested that some proteins have kinetic intermediates with a non-native structure. A simple G Ì o model does not explain such non-native intermediates. Therefore, the folding energy landscape of proteins with non-native intermediates should have characteristic properties. To identify such properties, we investigated the folding of bovine ß-lactoglobulin (ßLG). This protein has an intermediate with a non-native α-helical structure, although its native form is predominantly composed of ß-structure. In this study, we prepared mutants whose α-helical and ß-sheet propensities are modified and observed their folding using a stopped-flow circular dichroism apparatus. One interesting finding was that E44L, whose ß-sheet propensity was increased, showed a folding intermediate with an amount of ß-structure similar to that of the wild type, though its folding took longer. Thus, the intermediate seems to be a trapped intermediate. The high α-helical propensity of the wild-type sequence likely causes the folding pathway to circumvent such time-consuming intermediates. We propose that the role of the non-native intermediate is to control the pathway at the beginning of the folding reaction.