BackgroundThe image formed by the eye's optics is inherently blurred by aberrations specific to an individual's eyes. We examined how visual coding is adapted to the optical quality of the eye.Methods and FindingsWe assessed the relationship between perceived blur and the retinal image blur resulting from high order aberrations in an individual's optics. Observers judged perceptual blur in a psychophysical two-alternative forced choice paradigm, on stimuli viewed through perfectly corrected optics (using a deformable mirror to compensate for the individual's aberrations). Realistic blur of different amounts and forms was computer simulated using real aberrations from a population. The blur levels perceived as best focused were close to the levels predicted by an individual's high order aberrations over a wide range of blur magnitudes, and were systematically biased when observers were instead adapted to the blur reproduced from a different observer's eye.ConclusionsOur results provide strong evidence that spatial vision is calibrated for the specific blur levels present in each individual's retinal image and that this adaptation at least partly reflects how spatial sensitivity is normalized in the neural coding of blur.

New multifocal phase designs aiming at expanding depth of focus in the presbyopic eye are presented. The designs consist of multiple radial or angular zones of different powers or of combined low- and high-order aberrations. Multifocal performance was evaluated in terms of the dioptric range for which the optical quality is above an appropriate threshold, as well as in terms of the area under the through-focus optical quality curves. For varying optical power designs optimal through-focus performance was found for a maximum of three to four zones. Furthermore adding more zones decreased the optical performance of the solution. Angular zone designs provided better multifocal performance (1.95 times on average) than radial zone designs with identical number of zones and the same power range. The optimal design (angular design with three zones) surpassed by 33% the multifocal performance of a bifocal angular zone design and by 32% a standard multifocal phase plate with induced spherical aberration only. By using combinations of low- and high-order aberrations the through-focus range can be extended further by another 0.5 D beyond that of the best design of varying optical power. These designs can be implemented in adaptive optics systems for testing their visual performance in subjects and converted into multifocal contact lenses, intraocular lenses, or presbyopic corneal laser ablation profiles.

The perceived focus of an image can be strongly biased by prior adaptation to a blurred or sharpened image. We examined whether these adaptation effects can occur for the natural patterns of retinal image blur produced by high-order aberrations (HOAs) in the optics of the eye. Focus judgments were measured for 4 subjects to estimate in a forced choice procedure (sharp/blurred) their neutral point after adaptation to different levels of blur produced by scaled increases or decreases in their HOAs. The optical blur was simulated by convolution of the PSFs from the 4 different HOA patterns, with Zernike coefficients (excluding tilt, defocus, and astigmatism) multiplied by a factor between 0 (diffraction limited) and 2 (double amount of natural blur). Observers viewed the images through an Adaptive Optics system that corrected their aberrations and made settings under neutral adaptation to a gray field or after adapting to 5 different blur levels. All subjects adapted to changes in the level of blur imposed by HOA regardless of which observer’s HOA was used to generate the stimuli, with the perceived neutral point proportional to the amount of blur in the adapting image.

Abstractα-Synuclein aggregation is a key driver of neurodegeneration in Parkinson’s disease and related syndromes. Accordingly, obtaining a molecule that targets α-synuclein toxic assemblies with high affinity is a long-pursued objective. Here, we exploit the biophysical properties of toxic oligomers and amyloid fibrils to identify a family of α-helical peptides that bind to these α-synuclein species with low nanomolar affinity, without interfering with the monomeric functional protein. This activity is translated into a high anti-aggregation potency and the ability to abrogate oligomer-induced cell damage. Using a structure-guided search we identify a human peptide expressed in the brain and the gastrointestinal tract with analogous binding, anti-aggregation, and detoxifying properties. The chemical entities we describe here may represent a therapeutic avenue for the synucleinopathies and are promising tools to assist diagnosis by discriminating between native and toxic α-synuclein species.

BackgroundThe visual system adjusts to changes in the environment, as well as to changes within the observer, adapting continuously to maintain a match between visual coding and visual environment. We evaluated whether the perception of oriented blur is biased by the native astigmatism, and studied the time course of the after-effects following spectacle correction of astigmatism in habitually non-corrected astigmats.Methods and FindingsWe tested potential shifts of the perceptual judgments of blur orientation in 21 subjects. The psychophysical test consisted on a single interval orientation identification task in order to measure the perceived isotropic point (astigmatism level for which the image did not appear oriented to the subject) from images artificially blurred with constant blur strength (B = 1.5 D), while modifying the orientation of the blur according to the axis of natural astigmatism of the subjects. Measurements were performed after neutral (gray field) adaptation on naked eyes under full correction of low and high order aberrations. Longitudinal measurements (up to 6 months) were performed in three groups of subjects: non-astigmats and corrected and uncorrected astigmats. Uncorrected astigmats were provided with proper astigmatic correction immediately after the first session. Non-astigmats did not show significant bias in their perceived neutral point, while in astigmatic subjects the perceived neutral point was significantly biased, typically towards their axis of natural astigmatism. Previously uncorrected astigmats shifted significantly their perceived neutral point towards more isotropic images shortly (2 hours) after astigmatic correction wear, and, once stabilized, remained constant after 6 months. The shift of the perceived neutral point after correction of astigmatism was highly correlated with the amount of natural astigmatism.ConclusionsNon-corrected astigmats appear to be naturally adapted to their astigmatism, and astigmatic correction significantly changes their perception of their neutral point, even after a brief period of adaptation.

We demonstrate that certain combinations of non-rotationally symmetric aberrations (coma and astigmatism) can improve retinal image quality over the condition with the same amount of astigmatism alone. Simulations of the retinal image quality in terms of Strehl Ratio, and measurements of Visual Acuity under controlled aberrations with adaptive optics were performed, varying defocus, astigmatism and coma. Astigmatism ranged between 0 and 1.5D. Defocus ranged typically between -1 and 1D. The amount of coma producing best retinal image quality (for a given relative angle between astigmatism and coma) was computed and the amount was found to be different from zero in all cases (except for 0D of astigmatism). For example, for a 6mm pupil, in the presence of 0.5D of astigmatism, a value of coma of 0.23mum produced (for best focus) a peak improvement in Strehl Ratio by a factor of 1.7, over having 0.5D of astigmatism alone. The improvement holds over a range of >1.5D of defocus and peak improvements were found for amounts of coma ranging from 0.15mum to 0.35mum. We measured VA under corrected high order aberrations, astigmatism alone (0.5D) and astigmatism in combination with coma (0.23mum), with and without adaptive optics correction of all the other aberrations, in two subjects. We found that the combination of coma with astigmatism improved decimal VA by a factor of 1.28 (28%) and 1.47 (47%) in both subjects, over VA with astigmatism alone when all the rest of aberrations were corrected. Nevertheless, in the presence of typical normal levels of HOA the effect of the coma/astigmatism interaction is considerably diminished.

Previous studies suggest that certain combinations of coma and astigmatism improve optical quality over astigmatism alone. We tested these theoretical predictions on 20 patients. Visual acuity (VA) was measured under best spherical correction for different conditions: low- and higher order aberrations corrected, in the presence of 0.5 D of induced astigmatism, and adding different amounts of coma to 0.5 D of astigmatism. Measurements were performed for different relative angles between coma and astigmatism and for selected conditions, also through-focus. Adding coma (0.23 μm for 6-mm pupil) to astigmatism resulted in a clear increase of VA in 6 subjects, consistently with theoretical optical predictions, while VA decreased when coma was added to astigmatism in 7 subjects. In addition, in the presence of astigmatism only, VA decreased more than 10% with respect to all aberrations corrected in 13 subjects, while VA was practically insensitive to the addition of astigmatism in 4 subjects. The effects were related to the presence of natural astigmatism and whether this was habitually corrected or uncorrected. The fact that the expected performance occurs mainly in eyes with no natural astigmatism suggests relevant neural adaptation effects in eyes normally exposed to astigmatic blur.

The extent of protein hydration modulates the free energy barrier of both heterogeneous and homogeneous α-synuclein nucleation, leading to the formation of distinct amyloid polymorphs depending on the water activity of the protein microenvironment.