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Dahlmann-Noor, A.

Publications and source records attributed to Dahlmann-Noor, A..

4 recordsLinked to original sources

Visual crowding in albinism: Evidence for a cortical sensory deficit with oculomotor influences

PurposeFoveal vision in individuals with albinism is impaired not only by reduced visual acuity but also by elevated crowding - the disruption of object recognition in clutter. Because albinism is characterised by both retinal underdevelopment and nystagmus (uncontrolled eye movements), it is unclear whether crowding is elevated primarily from image motion due to eye movements or an additional sensory deficit. To disentangle these factors, we examined the spatial and featural selectivity of foveal crowding in albinism, comparing performance with controls and prior data from individuals with idiopathic infantile nystagmus syndrome (IINS), where nystagmus occurs without retinal underdevelopment. MethodsAdults with albinism (n=8) and age-matched controls (n=8; 19-49 years) identified the orientation of foveal Landolt-C targets. In Experiment 1, targets were presented alone or flanked horizontally or vertically to assess spatial selectivity. In Experiment 2, flankers were of the same or opposite contrast polarity to assess featural selectivity. Stimulus size was adaptively scaled using QUEST to estimate gap-size thresholds. ResultsCrowding was substantially elevated in albinism, relative to both controls and IINS. Experiment 1 revealed stronger crowding for horizontally than vertically positioned flankers in albinism, mirroring the predominant direction of nystagmic eye movements. In Experiment 2, opposite-polarity flankers did not reduce crowding, indicating an absence of selectivity for target-flanker similarity. ConclusionsFoveal crowding in albinism is markedly elevated, with a nystagmus-related spatial anisotropy and a lack of featural selectivity. These characteristics suggest that these elevations reflect both retinal image motion and a substantial sensory deficit arising from abnormal visual development.

neuroscience↗

Dopamine selectively regulates pediatric sclera/choroid interactions through the stimulation of exosome-associated retinoic acid

Postnatal eye growth is critical for healthy vision and yet, how this process is regulated at the cellular level is still unclear. The choroid is thought to play a crucial role in relaying signals from the retina to the sclera to modulate eye growth, but which cells are targeted and how they interact is not known. Using primary cultures of pediatric and adult human choroid and sclera stromal fibroblasts, we investigated the effect of choroid-conditioned medium (CCM) on scleral fibroblasts contractile activity. We show that CCM activates pediatric scleral fibroblast contraction, with age and antero-posterior location differences. Upon exposure to dopamine, a known negative regulator of eye growth, pediatric - but not adult - choroid cells lose their ability to stimulate scleral fibroblasts. Using RNA-Sequencing, we show that dopamine stimulates pathways linked to ribosomal activation, translation and exosome release exclusively in pediatric choroid cells. Removing exosomes from the CCM rescued the ability of dopamine-treated choroid cells to stimulate scleral fibroblasts. We further identify retinoic acid as the active exosome-associated compound preventing scleral fibroblast activation. Mechanistically, we show that CCM stimulates actomyosin-mediated protrusive activity in scleral fibroblasts. This is prevented when scleral cells are exposed to dopamine-CCM, and fully rescued upon exosome removal or ALDH1 inhibition. We thus propose that pediatric choroid stromal cells specifically relay dopamine-mediated retinal signals to the sclera during post-natal eye growth, operating through changes in secretome - including the production of exosome-associated retinoic acid - rather than gene expression changes. SIGNIFICANCEEye size is critical to optimal vision but the exact cellular and molecular mechanisms regulating it are still unknown. Failure to properly regulate postnatal eye growth leads to elongated eyes and myopia. Myopia is expected to affect half of the world population by 2050, with many at risk of blinding complications. Eye growth and homeostasis are supported by the sclera and the choroid, but how the two tissues interact to regulate eye growth is unknown. We use here human cells to demonstrate direct, age-specific, interactions between the two cell types and provide a rationale for the known negative effect of dopamine on eye growth, with significant implications for future studies as well as for the understanding and treatment of myopia.

cell biology↗

Late- but not early-onset blindness impairs the development of audio-haptic multisensory integration

Integrating different senses to reduce sensory uncertainty and increase perceptual precision can have an important compensatory function for individuals with visual impairment and blindness. However, how visual impairment and blindness impact the development of optimal multisensory integration in the remaining senses is currently unknown. Here we first examined how audio-haptic integration develops and changes across the life span in 92 sighted (blindfolded) individuals between 7 to 70 years of age by using a child-friendly size discrimination task. We assessed whether audio-haptic performance resulted in a reduction of perceptual uncertainty compared to auditory-only and haptic-only performance as predicted by maximum-likelihood estimation model. We then tested how this ability develops in 28 children and adults with different levels of visual experience, focussing on low vision individuals, and blind individuals that lost their sight at different ages during development. Our results show that in sighted individuals, adult-like audio-haptic integration develops around 13-15 years of age, and remains stable until late adulthood. While early blind individuals, even at the youngest ages, integrate audio-haptic information in an optimal fashion, late blind individuals do not. Optimal integration in low vision individuals follows a similar developmental trajectory as that of sighted individuals. These findings demonstrate that visual experience is not necessary for optimal audio-haptic integration to emerge, but that consistency of sensory information across development is key for the functional outcome of optimal multisensory integration.\n\nResearch HighlightsO_LIAudio-haptic integration follows principles of statistical optimality in sighted adults, remaining stable until at least 70 years of life\nC_LIO_LINear-optimal audio-haptic integration develops at 13-15 years in sighted adolescents\nC_LIO_LIBlindness within the first 8 years of life facilitates the development of optimal audio-haptic integration while blindness after 8 years impairs such development\nC_LIO_LISensory consistency in early childhood is crucial for the development of optimal multisensory integration in the remaining senses\nC_LI

neuroscience↗

A comparison of tests for quantifying sensory eye dominance

Clinicians rely heavily on stereoacuity to measure binocular visual function, but stereo-vision represents only one aspect of binocularity. Lab-based tests of sensory eye dominance (SED) are commonplace, but have not been translated to wider clinical practice. Here we compare several methods of quantifying SED in a format suitable for clinical use. We tested 30 participants with ostensibly normal vision on 8 tests. Seven tests (#1-7) were designed to quantify SED in the form of an interocular balance-point (BP). In tests #1-6, we estimated a contrast-BP, the interocular difference in contrast required for observers to be equally likely to base their judgement on either eye, whereas in test #7 we measured binocular rivalry (interocular ratio of sensory dominance duration). We compare test-retest reliability (intra-observer consistency) and test-validity (inter-observer discriminatory power) and compare BP to stereoacuity (test #8). The test that best preserved inter-observer differences in contrast balance while maintaining good test-retest reliability was a polarity judgement using superimposed opposite-contrast polarity same-identity optotypes. A reliable and valid measure of SED can be obtained rapidly (20 trials) using a simple contrast-polarity judgement. Tests that use polarity-rivalrous stimuli elicit more reliable judgments than those that do not.\n\nSignificance StatementAlthough sensory eye dominance is central to understanding normal and disordered binocular vision, there is currently no consensus as to the best way to measure it. Here we compare several candidate measures of sensory eye dominance and conclude that a reliable measure of SED can be achieved rapidly using a judgement of stimulus contrast-polarity.

neuroscience↗