Glaucoma is the leading cause of irreversible blindness worldwide but the effect of glaucoma on patients’ vision under suprathreshold conditions relevant to their natural visual environment is poorly understood. This project aimed to investigate and further understand the effects of glaucoma on three aspects of suprathreshold vision; apparent contrast of suprathreshold stimuli, detection and discrimination of image blur and crowding of peripheral vision. Psychophysical methods were employed to assess these three visual functions by measuring contrast matches of Gabor stimuli, blur detection and discrimination thresholds of edge stimuli and crowding ratios of Vernier targets. These measures were obtained from glaucoma observers tested within and outside of visual field defects and the data compared with healthy controls. Contrast matching ratios were similar between glaucoma and healthy age similar controls despite sensitivity loss in the glaucoma group. Blur detection and discrimination thresholds were similar between glaucoma observers’ tested within and outside of visual field defects and age-similar controls, though thresholds were slightly elevated for high contrast stimuli in the glaucoma visual field defect group. Crowding ratios were similar between participants with glaucoma and healthy young controls. The results demonstrate that aspects of suprathreshold visual function can be maintained in early glaucoma despite sensitivity loss at threshold. The results provide empirical evidence as to the asymptomatic nature of the disease in its early stages. It appears that in early glaucoma, there may be compensatory mechanisms at work within the visual system under suprathreshold conditions that can overcome loss of sensitivity at threshold. / The College of Optometrists

Yes / PURPOSE. Glaucoma raises contrast detection thresholds, but our natural visual environment is dominated by high contrast that may remain suprathreshold in early to moderate glaucoma. This study investigates the effect of glaucoma on the apparent contrast of visible stimuli. METHODS. Twenty participants with glaucoma with partial visual field defects (mean age, 72 ± 7 years) and 20 age-similar healthy controls (mean age, 70 ± 7 years) took part. Contrast detection thresholds for Gabor stimuli (SD, 0.75°) of four spatial frequencies (0.5, 1.0, 2.0, and 4.0 c/deg) were first measured at 10° eccentricity, both within and outside of visual field defects for participants with glaucoma. Subsequently, the contrast of a central Gabor was matched to that of a peripheral Gabor with contrast fixed at two times or four times the detection threshold. Data were analyzed by linear mixed modelling. RESULTS. Compared with controls, detection thresholds for participants with glaucoma were raised by 0.05 ± 0.025 (Michelson units, ± SE; P = 0.12) and by 0.141 ± 0.026 (P < 0.001) outside and within visual field defects, respectively. For reference stimuli at two times the detection contrast, matched contrast ratios (matched/reference contrast) were 0.16 ± 0.039 (P < 0.001) higher outside compared with within visual field defects in participants with glaucoma. Matched contrast ratios within visual field defects were similar to controls (mean 0.033 ± 0.066 lower; P = 0.87). For reference stimuli at four times the detection contrast, matched contrast ratios were similar across all three groups (P = 0.58). Spatial frequency had a minimal effect on matched contrast ratios. CONCLUSIONS. Despite decreased contrast sensitivity, people with glaucoma perceive the contrast of visible suprathreshold stimuli similarly to healthy controls. These results suggest possible compensation for sensitivity loss in the visual system. / Supported by a College of Optometrists PhD Scholarship. / Research Development Fund Publication Prize Award winner, June 2020

<div>Large protein molecules are abundant in biological cells but are very difficult to study in physiological conditions due to molecular disorder. For large proteins, most structural information is obtained in crystalline states which can be achieved in certain conditions at very low temperature. X-ray and neutron crystallography methods can then be used for determination of crystalline structures at atomic level. However, in solution at room or physiological temperatures such highly resolved descriptions cannot be obtained except in very few cases. Scattering methods that can be used to study this type of structures at room temperature include small-angle x-ray and neutron scattering. These methods are used here to study two distinct proteins that are both classified as glycoproteins, which are a large class of proteins with diverse biological functions. In this study, two specific plasma glycoproteins were used: Fibrinogen (340 kDa) and Alpha 1-Antitrypsin or A1AT (52 kDa). These proteins have been chosen based on the fact that they have a propensity to form very large molecular aggregates due to their tendency to polymerize. One goal of this project is to show that for such complex structures, a combination of scattering methods that include SAXS, SANS, and DLS can address important structural and interaction questions despite the fact that atomic resolution cannot be obtained as in crystallography. A1AT protein has been shown to have protective roles of lung cells against emphysema, while fibrinogen is a major factor in the blood clotting process. A systematic approach to study these proteins interactions with lipid membranes and other proteins, using contrast-matching small-angle neutron scattering (SANS), small angle x-ray scattering (SAXS) and dynamic light scattering (DLS), is presented here. A series of structural reference points for each protein in solution were determined by performing measurements under osmotic stress controlled by the addition of polyethylene glycol-1,500 MW (PEG 1500) in the samples. Osmotic pressure changes the free energy of the molecular mixture and has consequences on the structure and the interaction of molecular aggregates. In particular, the measured radius of gyration (Rg) for A1AT shows a sharp structural transition when the concentration of PEG 1500 is between 33 wt\% and 36 wt\%. Similarly, a significant structural change was observed for fibrinogen when the concentration of PEG 1500 was above 40 wt\%. This analysis is applied to a study of A1AT interacting with lipid membranes and to a study of fibrinogen polymerization in the presence of the enzyme thrombin, which catalyzes the formation of blood clots. The experimental approach presented here and the applications to specific questions show that an appropriate combination of scattering methods can produce useful information on the behavior and the interactions of large protein systems in physiological conditions despite the lower resolution compared to crystallography.</div>