Optometry and Vision Sciences - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 205
-
ItemImplantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats(JOURNAL OF VISUALIZED EXPERIMENTS, 2016-06-01)The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub-conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data.
-
ItemAAV-Mediated CRISPR/Cas Gene Editing of Retinal Cells In Vivo(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-06)PURPOSE: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) has recently been adapted to enable efficient editing of the mammalian genome, opening novel avenues for therapeutic intervention of inherited diseases. In seeking to disrupt yellow fluorescent protein (YFP) in a Thy1-YFP transgenic mouse, we assessed the feasibility of utilizing the adeno-associated virus 2 (AAV2) to deliver CRISPR/Cas for gene modification of retinal cells in vivo. METHODS: Single guide RNA (sgRNA) plasmids were designed to target YFP, and after in vitro validation, selected guides were cloned into a dual AAV system. One AAV2 construct was used to deliver Streptococcus pyogenes Cas9 (SpCas9), and the other delivered sgRNA against YFP or LacZ (control) in the presence of mCherry. Five weeks after intravitreal injection, retinal function was determined using electroretinography, and CRISPR/Cas-mediated gene modifications were quantified in retinal flat mounts. RESULTS: Adeno-associated virus 2-mediated in vivo delivery of SpCas9 with sgRNA targeting YFP significantly reduced the number of YFP fluorescent cells of the inner retina of our transgenic mouse model. Overall, we found an 84.0% (95% confidence interval [CI]: 81.8-86.9) reduction of YFP-positive cells in YFP-sgRNA-infected retinal cells compared to eyes treated with LacZ-sgRNA. Electroretinography profiling found no significant alteration in retinal function following AAV2-mediated delivery of CRISPR/Cas components compared to contralateral untreated eyes. CONCLUSIONS: Thy1-YFP transgenic mice were used as a rapid quantifiable means to assess the efficacy of CRISPR/Cas-based retinal gene modification in vivo. We demonstrate that genomic modification of cells in the adult retina can be readily achieved by viral-mediated delivery of CRISPR/Cas.
-
ItemAAV-mediated gene delivery of the calreticulin anti-angiogenic domain inhibits ocular neovascularization(SPRINGER, 2018-02)Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. The expression of CAD180 and CAD112 was elevated in human umbilical vein endothelial cells transduced with scAAV2-CAD180 or scAAV2-CAD112, respectively, and both inhibited angiogenic activity in vitro. Intravitreal gene delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly inhibited ischemia-induced retinal neovascularization in rat eyes (CAD180: 52.7% reduction; CAD112: 49.2% reduction) compared to scAAV2-mCherry, as measured in retinal flatmounts stained with isolectin B4. Moreover, the retinal structure and function were unaffected by scAAV2-CAD180 or scAAV2-CAD112, as measured by optical coherence tomography and electroretinography. Moreover, subretinal delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly attenuated laser-induced choroidal neovascularization in mouse eyes compared to scAAV2-mCherry, as measured by fundus fluorescein angiography (CAD180: 62.4% reduction; CAD112: 57.5% reduction) and choroidal flatmounts (CAD180: 40.21% reduction; CAD112: 43.03% reduction). Gene delivery using scAAV2-CAD180 or scAAV2-CAD112 has significant potential as a therapeutic option for the management of ocular neovascularization.
-
ItemA Model of Glaucoma Induced by Circumlimbal Suture in Rats and Mice(Journal of Visualized Experiments, 2018)The circumlimbal suture is a technique for inducing experimental glaucoma in rodents by chronically elevating intraocular pressure (IOP), a well-known risk factor for glaucoma. This protocol demonstrates a step-by-step guide on this technique in Long Evans rats and C57BL/6 mice. Under general anesthesia, a "purse-string" suture is applied on the conjunctiva, around the equator and behind the limbus of the eye. The fellow eye serves as an untreated control. Over the duration of our study, which was a period of 8 weeks for rats and 12 weeks for mice, IOP remained elevated, as measured regularly by rebound tonometry in conscious animals without topical anesthesia. In both species, the sutured eyes showed electroretinogram features consistent with preferential inner retinal dysfunction. Optical coherence tomography showed selective thinning of the retinal nerve fiber layer. Histology of the rat retina in cross-section found reduced cell density in the ganglion cell layer, but no change in other cellular layers. Staining of flat-mounted mouse retinae with a ganglion cell specific marker (RBPMS) confirmed ganglion cell loss. The circumlimbal suture is a simple, minimally invasive and cost-effective way to induce ocular hypertension that leads to ganglion cell injury in both rats and mice.
-
ItemTowards better estimates of uncorrected presbyopia(WORLD HEALTH ORGANIZATION, 2015-10)
-
ItemFunctional screening devices for diabetic retinopathy(WILEY, 2018-07)
-
ItemAttentional asymmetry between visual hemifields is related to habitual direction of reading and its implications for debate on cause and effects of dyslexia(WILEY, 2018-02)A major controversy regarding dyslexia is whether any of the many visual and phonological deficits found to be correlated with reading difficulty cause the impairment or result from the reduced amount of reading done by dyslexics. We studied this question by comparing a visual capacity in the left and right visual hemifields in people habitually reading scripts written right-to-left or left-to-right. Selective visual attention is necessary for efficient visual search and also for the sequential recognition of letters in words. Because such attentional allocation during reading depends on the direction in which one is reading, asymmetries in search efficiency may reflect biases arising from the habitual direction of reading. We studied this by examining search performance in three cohorts: (a) left-to-right readers who read English fluently; (b) right-to-left readers fluent in reading Farsi but not any left-to-right script; and (c) bilingual readers fluent in English and in Farsi, Arabic, or Hebrew. Left-to-right readers showed better search performance in the right hemifield and right-to-left readers in the left hemifield, but bilingual readers showed no such asymmetries. Thus, reading experience biases search performance in the direction of reading, which has implications for the cause and effect relationships between reading and cognitive functions.
-
ItemThe effect of blue-light blocking spectacle lenses on visual performance, macular health and the sleep-wake cycle: asystematic review of the literature(WILEY, 2017-11)PURPOSE: Blue-blocking (BB) spectacle lenses, which attenuate short-wavelength light, are being marketed to alleviate eyestrain and discomfort when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. The aim of this review was to investigate the relative benefits and potential harms of these lenses. METHODS: We included randomised controlled trials (RCTs), recruiting adults from the general population, which investigated the effect of BB spectacle lenses on visual performance, symptoms of eyestrain or eye fatigue, changes to macular integrity and subjective sleep quality. We searched MEDLINE, EMBASE, the Cochrane Library and clinical trial registers, until 30 April 2017. Risk of bias was assessed using the Cochrane tool. RESULTS: Three studies (with 136 participants) met our inclusion criteria; these had limitations in study design and/or implementation. One study compared the effect of BB lenses with clear lenses on contrast sensitivity (CS) and colour vision (CV) using a pseudo-RCT crossover design; there was no observed difference between lens types (log CS; Mean Difference (MD) = -0.01 [-0.03, 0.01], CV total error score on 100-hue; MD = 1.30 [-7.84, 10.44]). Another study measured critical fusion frequency (CFF), as a proxy for eye fatigue, on wearers of low and high BB lenses, pre- and post- a two-hour computer task. There was no observed difference between low BB and standard lens groups, but there was a less negative change in CFF between the high and low BB groups (MD = 1.81 [0.57, 3.05]). Both studies compared eyestrain symptoms with Likert scales. There was no evidence of inter-group differences for either low BB (MD = 0.00 [-0.22, 0.22]) or high BB lenses (MD = -0.05 [-0.31, 0.21]), nor evidence of a difference in the proportion of participants showing an improvement in symptoms of eyestrain or eye fatigue. One study reported a small improvement in sleep quality in people with self-reported insomnia after wearing high compared to low-BB lenses (MD = 0.80 [0.17, 1.43]) using a 10-point Likert scale. A study involving normal participants found no observed difference in sleep quality. We found no studies investigating effects on macular structure or function. CONCLUSIONS: We find a lack of high quality evidence to support using BB spectacle lenses for the general population to improve visual performance or sleep quality, alleviate eye fatigue or conserve macular health.
-
ItemOptical coherence tomography predicts 4-year incident diabetic neuropathy(WILEY, 2017-07)PURPOSE: To examine the capability of optical coherence tomography-derived retinal thickness measures in detecting 4-year incident diabetic peripheral neuropathy (DPN). METHODS: 145 eyes of 145 participants with diabetes but no DPN at baseline were examined for incident DPN. HbA1c levels, nephropathy, neuropathy (DPN), cardiovascular measures, and various retinal thickness measures were examined at baseline and after 4 years. Incidence of DPN was defined as newly developed DPN at follow-up. Baseline factors were assessed by univariate and a step-wise multiple logistic regression, and the predictors were examined for diagnostic capabilities. RESULTS: Of the 145 participants without DPN at baseline, 51 had developed DPN when examined after 4 years (35% incidence). Of the ophthalmic variables, the mean (S.D.) of the overall thickness in the parafovea at baseline was 315 (18) μm in the no DPN group and 306 (18) μm in the 'incidence' group, and the differences were significant, p = 0.005. The superior hemisphere parafovea (mean (S.D.): 318 (17) μm vs 310 (20) μm, p = 0.02) and inferior hemisphere parafovea (313 (19) μm vs 302 (18) μm, p = 0.002) were different in the incident DPN group compared with the no DPN group. When adjusted for age, retinal thickness in the parafovea (AUC = 0.65, p = 0.003, 86% sensitivity and 44% specificity at 321 μm criterion), and body mass index or BMI (AUC = 0.65, p = 0.003, 49% sensitivity and 83% specificity at 29.3 kg m-2 criterion) at baseline were significant predictors for 4-year incident DPN. CONCLUSIONS: A lower retinal thickness at the parafovea and a higher BMI can predict 4-year incident neuropathy in patients with diabetes, with acceptable diagnostic accuracies. This OCT-derived measure may serve as a potential ophthalmic marker in the screening of patients at risk of developing DPN.
-
Item