Human induced pluripotent stem cells generate light responsive retinal organoids with variable and nutrient dependent efficiency

The availability of in vitro models of the human retina in which to perform pharmacological and toxicological studies is an urgent and unmet need. An essential step for developing in vitro models of human retina is the ability to generate laminated, physiologically functional and light-responsive retinal organoids from renewable and patient specific sources. We investigated five different human induced pluripotent stem cell (iPSC) lines and showed a significant variability in their efficiency to generate retinal organoids. Despite this variability, by month 5 of differentiation, all iPSC-derived retinal organoids were able to generate light responses, albeit immature, comparable to the earliest light responses recorded from the neonatal mouse retina, close to the period of eye opening. All iPSC-derived retinal organoids exhibited at this time a well-formed outer nuclear like layer containing photoreceptors with inner segments, connecting cilium and outer like segments. The differentiation process was highly dependent on seeding cell density and nutrient availability determined by factorial experimental design. We adopted the differentiation protocol to a multiwell plate format which enhanced generation of retinal organoids with retinal pigmented epithelium (RPE) and improved ganglion cell development and the response to physiological stimuli. We tested the response of iPSC-derived retinal organoids to Moxifloxacin and showed that similarly to in vivo adult mouse retina, the primary affected cell types were photoreceptors. Together our data indicate that light responsive retinal organoids derived from carefully selected and differentiation efficient iPSC lines can be generated at the scale needed for pharmacology and drug screening purposes. © AlphaMed Press 2018

Automated diagnosis of referable maculopathy in diabetic retinopathy screening

This paper introduces an algorithm for the automated diagnosis of referable maculopathy in retinal images for diabetic retinopathy screening. Referable maculopathy is a potentially sight-threatening condition requiring immediate referral to an ophthalmologist from the screening service, and therefore accurate referral is extremely important. The algorithm uses a pipeline of detection and filtering of peak points with strong local contrast, segmentation of candidate lesions, extraction of features and classification by a multilayer perceptron. The optic nerve head and fovea are detected, so that the macula region can be identified and scanned. The algorithm is assessed against a reference standard database drawn from the Birmingham City Hospital (UK) diabetic retinopathy screening programme, against two possible modes of use: independent screening, and pre-filtering to reduce human screener workload.</p

Percentage of women ever having had a mammogram, NBCC Breast Health Survey 2003

<p><b>Copyright information:</b></p><p>Taken from "The 2003 Australian Breast Health Survey: survey design and preliminary results"</p><p>http://www.biomedcentral.com/1471-2458/8/13</p><p>BMC Public Health 2008;8():13-13.</p><p>Published online 14 Jan 2008</p><p>PMCID:PMC2248181.</p><p></p