Optometry and Vision Sciences - Research Publications
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ItemAge-Specific Retinal and Cerebral Immunodetection of Amyloid-β Plaques and Oligomers in a Rodent Model of Alzheimer's Disease(IOS PRESS, 2020)BACKGROUND: Amyloid-β soluble oligomers (Aβo) are believed to be the cause of the pathophysiology underlying Alzheimer's disease (AD) and are normally detected some two decades before clinical onset of the disease. Retinal pathology associated with AD pathogenesis has previously been reported, including ganglion cell loss, accumulation of Aβ deposits in the retina, and reduction of nerve fiber layer thickness as well as abnormalities of the microvasculature. OBJECTIVE: This study's aim is to better understand the relationship between brain and retinal Aβo deposition and in particular to quantify levels of the toxic Aβo as a function of age in the retina of a rodent model of AD. METHODS: Retinas and brain tissue from 5×FAD mice were stained with Congo red, Thioflavin-T (Th-T), and Aβ plaque-specific and Aβo-specific antibodies. RESULTS: We show that retinas displayed an age-dependent increase of Th-T-specific amyloid fibrils. Staining with anti-Aβ antibody confirmed the presence of the Aβ plaques in all 5×FAD retinas tested. In contrast, staining with anti-Aβo antibody showed an age-dependent decrease of retinal Aβo. Of note, Aβo was observed mainly in the retinal nuclear layers. Finally, we confirmed the localization of Aβo to neurons, typically accumulating in late endosomes, indicating possible impairment of the endocytic pathway. CONCLUSION: Our results demonstrate the presence of intraneuronal Aβo in the retina and its accumulation inversely correlated with retinal Aβ plaque deposition, indicating an age-related conversion in this animal model. These results support the development of an early AD diagnostic test targeting Aβo in the eye.
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ItemPotential mechanisms of retinal ganglion cell type-specific vulnerability in glaucoma(WILEY, 2020-09)Glaucoma is a neurodegenerative disease characterised by progressive damage to the retinal ganglion cells (RGCs), the output neurons of the retina. RGCs are a heterogenous class of retinal neurons which can be classified into multiple types based on morphological, functional and genetic characteristics. This review examines the body of evidence supporting type-specific vulnerability of RGCs in glaucoma and explores potential mechanisms by which this might come about. Studies of donor tissue from glaucoma patients have generally noted greater vulnerability of larger RGC types. Models of glaucoma induced in primates, cats and mice also show selective effects on RGC types - particularly OFF RGCs. Several mechanisms may contribute to type-specific vulnerability, including differences in the expression of calcium-permeable receptors (for example pannexin-1, P2X7, AMPA and transient receptor potential vanilloid receptors), the relative proximity of RGCs and their dendrites to blood supply in the inner plexiform layer, as well as differing metabolic requirements of RGC types. Such differences may make certain RGCs more sensitive to intraocular pressure elevation and its associated biomechanical and vascular stress. A greater understanding of selective RGC vulnerability and its underlying causes will likely reveal a rich area of investigation for potential treatment targets.
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ItemLongitudinal outcomes of circumlimbal suture model-induced chronic ocular hypertension in Sprague-Dawley albino rats(SPRINGER, 2020-12)PURPOSE: To characterise longitudinal structural and functional changes in albino Sprague-Dawley rats following circumlimbal suture ocular hypertension (OHT) induction. METHODS: Ten-week-old rats (n = 24) underwent suture implantation around the limbal region in both eyes. On the next day, the suture was removed from one eye (control eyes) and left intact in the other eye (OHT eyes) of each animal. Intraocular pressure (IOP) was monitored weekly twice for the next 15 weeks. Optical coherence tomography (OCT) and electroretinogram (ERG) were measured at baseline and weeks 4, 8, 12, and 15, and eyes were then collected for histological assessment. RESULTS: Sutured eyes (n = 12) developed IOP elevation of ~ 50% in the first 2 weeks that was sustained at ~ 25% above the control eye up to week 15 (p = 0.001). Animals with insufficient IOP elevation (n = 6), corneal changes (n = 3), and attrition (n = 3) were excluded from the analysis. OHT eyes developed significant retinal nerve fibre layer (RNFL) thinning (week 4: - 19 ± 14%, p = 0.10; week 8: - 17 ± 12%, p = 0.04; week 12: - 16 ± 10%, p = 0.04, relative to baseline) and reduction in retinal ganglion cell (RGC) density (- 32 ± 26%, p = 0.02). At week 15, both inner (9 ± 7%, p = 0.01) and outer retinal layer thicknesses (6.0 ± 5%, p = 0.001) showed a mild increase in thicknesses. The positive scotopic threshold response (- 28 ± 25%, p = 0.04) and a-wave were significantly reduced at week 12 (- 35 ± 21%; p = 0.04), whereas b-wave was not significantly affected (week 12: - 18 ± 27%, p = 0.24). CONCLUSION: The circumlimbal suture model produced a chronic, moderate IOP elevation in an albino strain that led to RNFL thinning and reduced RGC density along with the reductions in ganglion and photoreceptoral cell functions. There was a small thickening in both outer and inner retinal layers.
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ItemGene Therapy Intervention in Neovascular Eye Disease: A Recent Update(CELL PRESS, 2020-10-07)Aberrant growth of blood vessels (neovascularization) is a key feature of severe eye diseases that can cause legal blindness, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). The development of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of ocular neovascularization. Novel proangiogenic targets, such as angiopoietin and platelet-derived growth factor (PDGF), are under development for patients who respond poorly to anti-VEGF therapy and to reduce adverse effects from long-term VEGF inhibition. A rapidly advancing area is gene therapy, which may provide significant therapeutic benefits. Viral vector-mediated transgene delivery provides the potential for continuous production of antiangiogenic proteins, which would avoid the need for repeated anti-VEGF injections. Gene silencing with RNA interference to target ocular angiogenesis has been investigated in clinical trials. Proof-of-concept gene therapy studies using gene-editing tools such as CRISPR-Cas have already been shown to be effective in suppressing neovascularization in animal models, highlighting the therapeutic potential of the system for treatment of aberrant ocular angiogenesis. This review provides updates on the development of anti-VEGF agents and novel antiangiogenic targets. We also summarize current gene therapy strategies already in clinical trials and those with the latest approaches utilizing CRISPR-Cas gene editing against aberrant ocular neovascularization.
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ItemScaling the size of perimetric stimuli reduces variability and returns constant thresholds across the visual field(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2020-10)The conventional stimulus for standard automated perimetry is fixed in size, giving elevated contrast thresholds and reduced test reliability in the periphery. Here, we test the hypothesis that appropriate scaling of the size of perimetric stimuli will return fixed thresholds and reduced variability across the visual field. We derived frequency-of-seeing (FOS) curves in five healthy subjects at central (3 degrees) and peripheral (27 degrees) locations with a method of constant stimuli (MOCS) using a desktop LCD display. FOS curves for a Goldmann III (GIII) stimulus were compared with those for size scaled spots. To consider clinical translation, we tested a further five healthy subjects (22-24 years) with the Melbourne Rapid Fields (MRF) tablet perimeter at several locations spanning 1 degree to 25 degrees from fixation, deriving FOS curves (MOCS) and also conducting repeated adaptive clinical thresholding to assess intra- and interobserver variability. We found that GIII contrast thresholds were significantly elevated in the periphery compared with the parafovea, with concomitant reduction of FOS slope. Using appropriately size scaled spots, threshold and slope differences between these locations were significantly reduced. FOS data collected with the tablet perimeter confirmed that size scaling confers broad equivalence of the shape of the FOS curve across the visual field. Repeated adaptive thresholding with size scaled stimuli gave relatively constant intra-observer variability across the visual field, which compares favorably with published normative data obtained with the GIII stimulus. The reduced variability will improve signal-to-noise ratio for correct classification of normal visual field test results, whereas the lower contrast thresholds yield greater dynamic range, which should improve the ability to reliably monitor moderate defects.
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ItemCorrelation of retinal changes with choroidal changes in acute and recurrent central serous chorioretinopathy assessed by swept-source optical coherence tomography.(SAGE Publications, 2020)PURPOSE: To evaluate affected choroidal regions and corresponding retinal changes in acute and recurrent central serous chorioretinopathy using swept-source optical coherence tomography. METHODS: The foveal and subfoveal choroidal thicknesses were measured with swept-source optical coherence tomography. The retina was divided into five zones on the swept-source optical coherence tomography image based on baseline choroidal thickness being <100, 100-199, 200-299, 300-399 and ⩾400 μm. The retinal and choroidal thicknesses in the same five regions were evaluated during follow-up. The measurements were then compared between baseline (when central serous chorioretinopathy was active) and follow-up (after complete resolution of disease). RESULTS: At baseline, in the acute group, the mean outer retinal layer thickness was significantly higher in areas with thicker choroid and lower in areas with thinner choroid. No such change was noticed in the recurrent group. In the acute group, the overall retinal thickness from baseline to follow-up decreased from 269.84 to 251.9 µm, ganglion cell layer thickness decreased from 107.14 to 101.28 µm, retinal nerve fibre layer thickness decreased from 56.96 to 49.33 µm, and no significant difference was noted in choroidal thickness. In the recurrent group, choroidal thickness significantly increased from 254.58 to 262.55 µm and ganglion cell layer decreased from 103.43 to 94.01 µm. No significant difference was noted in overall retina and retinal nerve fibre layer. Reduction in choroidal and retinal layer thicknesses was better in eyes which underwent laser treatment than the observation group. CONCLUSION: Swept-source optical coherence tomography might serve as an important non-invasive tool for both evaluating the extent of pathology and to predict the recurrence rate.
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ItemNo Preview AvailableCentral and peripheral motion perception under mesopic conditions in older adults(Association for Research in Vision and Ophthalmology (ARVO), 2020-10-20)
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ItemHigh Fidelity Bidirectional Neural Interfacing with Carbon Fiber Microelectrodes Coated with Boron-Doped Carbon Nanowalls: An Acute Study(WILEY-V C H VERLAG GMBH, 2020-12)Abstract Implantable electrodes that can communicate with a small, selective group of neurons via both neural stimulation and recording are critical for the development of advanced neuroprosthetic devices. Microfiber electrodes with neuron‐scale cross‐sections have the potential to improve the spatial resolution for both stimulation and recording, while minimizing the chronic inflammation response after implantation. In this work, glass insulated microfiber electrodes are fabricated by coating carbon fibers with boron‐doped carbon nanowalls. The coating significantly improves the electrochemical properties of carbon fibers, leading to a charge injection capacity of 7.82 ± 0.35 mC cm−2, while retaining good flexibility, stability and biocompatibility. When used for neural interfacing, the coated microelectrodes successfully elicit localized stimulation responses in explanted retina, and are also able to detect signals from single neurons, in vivo with a signal‐to‐noise ratio as high as 6.7 in an acute study. This is the first report of using carbon nanowall coated carbon fibers for neural interfacing.
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ItemEye movements in anorexia nervosa: State or trait markers?(WILEY, 2020-10)OBJECTIVE: Differences in saccadic eye movements are widely reported in mental illnesses, and can indirectly inform our understanding of neurobiological and cognitive underpinnings of psychiatric conditions, including anorexia nervosa (AN). Preliminary research has suggested that individuals with AN may show specific eye movement abnormalities; whether these deficits are representative of state or trait effects is, however, unclear. The aim of this study was to identify whether there are demonstrable differences in performance on saccadic eye movement tasks in individuals with current AN (c-AN), those who are weight-restored from AN (wr-AN), biological sisters of individuals with AN (AN-sis), and healthy controls (HC). METHODS: Eighty participants took part in the study (n = 20/group). A set of saccadic eye movement tasks was administered, including prosaccade, antisaccade, memory-guided saccade, and visual scanpath tasks. RESULTS: The c-AN group showed an increased rate of inhibitory errors to 10° targets on the memory-guided saccade task. DISCUSSION: The results are discussed in terms of the potential role of the superior colliculus in AN, and that the findings may reflect a state measure of AN.