Diabetologie und Stoffwechsel 2018; 13(S 01): S45
DOI: 10.1055/s-0038-1641889
Poster
Komplikationen II
Georg Thieme Verlag KG Stuttgart · New York

H3K36me3 associated pericyte loss in early diabetic retinopathy

K Kohl
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany, Mannheim, Germany
,
M Kolibabka
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany, Mannheim, Germany
,
P Friedrichs
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany, Mannheim, Germany
,
HP Hammes
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2018 (online)

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    Pericyte loss is one of the earliest vascular signs of diabetic retinopathy. Capillaries are hereby destabilized leading to vasoregression during the course of the disease.

    Gene expression changes of microarray analyses of a streptozotocin-induced diabetic mouse model point towards a distinct state of H3K36 trimethylation in the retina as early as six weeks of diabetes. The epigenetic modification H3K36me3 regulates chromatin transcription and occurs on constituous as well as facultative heterochromatin.

    The exact mechanisms for pericyte dropout and incipient diabetic retinopathy are not yet fully understood and need further clarification. We investigated H3K36me3 as an early mechanism in relation to pericyte loss.

    Pericyte numbers were determined in retinal digests by quantitative morphometry. H3K36me3 was measured photometrically in an immune-based assay.

    After 12 weeks of STZ-Diabetes, pericyte count of diabetic animals was lower than in normoglycemic animals (NC: 1571 ± 69.80 vs. DC: 1978 ± 93.52; p < 0.01; [pericytes/mm2]; n = 6). After six weeks of STZ-diabetes, levels of H3K36me3 were higher in diabetic than in normoglycemic mice persisting until week 12 (6w: 1.69 vs. 1.00; p < 0.0001; 12w: 2.18 vs. 2.69; p < 0.05; [fold change of NC 6w]; n = 6).

    These findings suggest that H3K36me3 is changed early during experimental diabetic retinopathy, which could lead to more severe signs of the disease.

    Further investigations will assess the pericyte status in this animal model after six weeks to establish a timely correlation between H3K36 trimethylation and pericyte loss in early diabetic retinopathy.


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