Outer Retinal Structure in Best Vitelliform Macular Dystrophy

Importance Demonstrating the utility of adaptive optics scanning light ophthalmoscopy (AOSLO) to assess outer retinal structure in Best vitelliform macular dystrophy (BVMD). Objective To characterize outer retinal structure in BVMD using spectral-domain optical coherence tomography (SD-OCT) and AOSLO. Design, Setting, and Participants Prospective, observational case series. Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee. Intervention Thickness of 2 outer retinal layers corresponding to photoreceptor inner and outer segments was measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in 2 subjects. Main Outcome and Measure Photoreceptor structure. Results Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size were consistent with Henle fibers. Conclusions and Relevance The AOSLO findings indicate that substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation

Using Evolutionary Conserved Modules in Gene Networks as a Strategy to Leverage High Throughput Gene Expression Queries

Background: Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seednetwork of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. Based on the evolutionary conservation of gene relationships, we test the hypothesis that a seed network derived from studies of retinal cell determination in the fly, Drosophila melanogaster, will be an effective way to identify novel candidate genes for their role in mouse retinal development. Methodology/Principal Findings: Our results demonstrate that a number of gene relationships regulating retinal cell differentiation in the fly are identifiable as pairwise correlations between genes from developing mouse retina. In addition, we demonstrate that our extracted seed-network of correlated mouse genes is an effective tool for querying datasets and provides a context to generate hypotheses. Our query identified 46 genes correlated with our extracted seed-network members. Approximately 54% of these candidates had been previously linked to the developing brain and 33% had been previously linked to the developing retina. Five of six candidate genes investigated further were validated by experiments examining spatial and temporal protein expression in the developing retina. Conclusions/Significance: We present an effective strategy for pursuing a systems biology approach that utilizes an evolutionary comparative framework between two model organisms, fly and mouse. Future implementation of this strategy will be useful to determine the extent of network conservation, not just gene conservation, between species and will facilitate the use of prior biological knowledge to develop rational systems-based hypotheses

Back problems, co-morbidities and their association with wealth

Background context: Studies assessing the economic burden of back problems have given little consideration to the presence of comorbidities.\ud \ud Purpose: To assess the difference in the value of wealth held by Australians who have back problems and varying numbers of chronic comorbidities.\ud \ud Study design: A cross-sectional study.\ud \ud Patient sample: Individuals aged 45 to 64 years in 2009: 4,388 with no chronic health conditions, 1,405 with back problems, and 3,018 with other health conditions.\ud \ud Outcome measure: Total wealth (cash, shares, superannuation, investment property, and owner occupied home).\ud \ud Methods: Using a microsimulation model (Health&WealthMOD), logistic regression models were used to assess the odds of having any wealth. Linear regression models were used to assess the difference in the value of this wealth.\ud \ud Results: Those with back problems and two comorbidities had 0.16 (95% confidence interval [CI]: 0.06–0.42) times the odds and those with back problems and three or more comorbidities had 0.20 (95% CI: 0.11–0.38) times the odds of having accumulated some wealth than those with no chronic health conditions. Those with back problems and three or more comorbidities had a median value of total wealth of around $150,000, whereas those with back problems only and back problems and one comorbidity had a median value of total wealth of around$250,500. There was no significant difference in the amount of wealth accumulated by those with back problems and at least one comorbidity and those with other health conditions and the same number of comorbidities. However, those with only one health condition (excluding back problems) had 65% more wealth than those with back problems only (95% CI: 5.1–161.2).\ud \ud Conclusions: This study highlights the importance of considering multiple morbidities when discussing the relationship between back problems and economic circumstances