Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy

Graham, Patricia; Kaidonis, Georgia; Abhary, Sotoodeh; Gillies, Mark C; Daniell, Mark; Essex, Rohan W.; Chang, John H; Lake, Stewart; Pal, Bishwanath; Jenkins, Alicia J.; Hewitt, Alex W.; Lamoureux, Ecosse L.; Hykin, Philip; Petrovsky, Nikolai; Brown, Matthew A.; Craig, Jamie E; Burdon, Kathryn P.

doi:10.1186/s12881-018-0587-8

Cited by 54 publications

(51 citation statements)

References 35 publications

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“…Patterns of expression differed, however, with PHGDH expressed primarily in foveal midget RGCS, LINC00461 primarily in foveal parasol RGCs, and PSPG and GBAS in both. MRPL19, one of the few genes implicated specifically in DME, which affects the fovea by clinical definition, was expressed preferentially in foveal RGCs(54).DISCUSSIONWe used high-throughput single-cell RNA-seq to generate a cell atlas of the adult human retina. From 55,736 foveal and 29,246 peripheral retinal cells, we identified 58 cell types.…”

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confidence: 99%

Cell Atlas of the Human Fovea and Peripheral Retina

Yan¹,

Peng

Zyl

et al. 2020

Preprint

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Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and nonneuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 2 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.

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confidence: 99%

Cell Atlas of the Human Fovea and Peripheral Retina

Yan¹,

Peng

Zyl

et al. 2020

Preprint

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“…The variability in the rate of progression to vision-threatening retinopathy and particularly in the response to treatment was noted from the onset of clinical and epidemiological studies in diabetic patients and has been attributed to the effect of genetic predisposition together with systemic and socioeconomic factors. Single-nucleotide polymorphisms [58][59][60] and genome-wide associations [61][62][63] have been investigated in patients with proliferative disease and macular edema, and the results so far are inconclusive mainly due to the size of the samples and the Diabetic Retinopathy and Blindness: An Epidemiological Overview DOI: http://dx.doi.org/10.5772/intechopen.88756 inclusion of cases with coexisting proliferations and edema in the cohorts. Detailed assessment in the polymorphisms of the VEGF gene revealed that some of them are related to higher susceptibility to severe retinopathy, but not to the outcome of ranibizumab intravitreal injections [64] in contrast to an earlier report on the response to bevacizumab [65].…”

Section: Progression To Vision-threatening Retinopathymentioning

confidence: 99%

Diabetic Retinopathy and Blindness: An Epidemiological Overview

Pandova¹

2020

Visual Impairment and Blindness - What We Know and What We Have to Know

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Prevalence of diabetes is rising worldwide. In the course of the last 20 years, blindness and low vision due to diabetic eye complications have increased in large regions in Eastern Europe, North Africa/Middle East, Asia, Latin America, and Oceania. The magnitude and trends of vision-threatening disease are presented. Systemic risk factors for progression to sight-threatening disease are reviewed. The impact of economic and cultural background on early diagnosis and adherence to treatment is highlighted. Current management of diabetic macular edema, proliferative diabetic retinopathy, neovascular glaucoma, and cataract surgery of diabetic patients is outlined, and its contribution to preventing vision loss is reviewed.

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“…As an example, the strongest known clinical risk factors for DR, duration of diabetes and glycaemic control (collectively glycaemic exposure), were estimated to contribute only a small proportion of the variation in risk in major clinical trials conducted in the United Kingdom and the United States [31]. Therefore, it is hypothesised that ethnic differences, environmental factors and genetic susceptibility could also play a role in DR progression, but whether genetic factors, or others, are intrinsically involved in the premature and severe vision impairment experienced by Indigenous Australians is as yet unknown [32]. It is important to search for all factors that contribute to DR risk, both biological and non-biological, to identify more complete social, clinical or biological markers that can be targets for intervention to prevent, delay or predict the progression of DR.…”

Section: Addressing the Knowledge Gapsmentioning

confidence: 99%

Working Towards Eye Health Equity for Indigenous Australians with Diabetes

Estevez

Howard

Craig

et al. 2019

IJERPH

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Type 2 diabetes mellitus (T2DM) poses significant challenges to individuals and broader society, much of which is borne by disadvantaged and marginalised population groups including Indigenous people. The increasing prevalence of T2DM among Indigenous people has meant that rates of diabetes-related complications such as blindness from end-stage diabetic retinopathy (DR) continue to be important health concerns. Australia, a high-income and resource-rich country, continues to struggle to adequately respond to the health needs of its Indigenous people living with T2DM. Trends among Indigenous Australians highlight that the prevalence of DR has almost doubled over two decades, and the prevalence of diabetes-related vision impairment is consistently reported to be higher among Indigenous Australians (5.2%-26.5%) compared to non-Indigenous Australians (1.7%). While Australia has collated reliable estimates of the eye health burden owing to T2DM in its Indigenous population, there is fragmentation of existing data and limited knowledge on the underlying risk factors. Taking a systems approach that investigates the social, environmental, clinical, biological and genetic risk factors, and-importantly-integrates these data, may give valuable insights into the most important determinants contributing to the development of diabetes-related blindness. This knowledge is a crucial initial step to reducing the human and societal impacts of blindness on Indigenous Australians, other priority populations and society at large.

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Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy

Cited by 54 publications

References 35 publications

Cell Atlas of the Human Fovea and Peripheral Retina

Cell Atlas of the Human Fovea and Peripheral Retina

Diabetic Retinopathy and Blindness: An Epidemiological Overview

Working Towards Eye Health Equity for Indigenous Australians with Diabetes

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