Introduction: What they say
A study from the Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; and German Centre for Cardiovascular Research (DZHK) partner site Rhein-Main, Germany shows that “Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy.” This research paper was published, in the 6 December 2017 issue of the journal “Nature” [One of the best research journals in “General Science” with an I.F of 43 plus], by Prof.Ingrid Fleming and Jiong Hu and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for Diabetic retinopathy: D-3 Hydroxybutyrate (D3HB) inhibits Soluble epoxide hydrolase (sEH) expression, decreases toxic 19,20-dihydroxydocosapentaenoic acid levels, inhibits pericyte loss, vascular permeability, and inflammation of the eye and progression of diabetic retinopathy, via down regulation of its target gene
From significance of the study to public health relevance:
Given that: (1) more than 422 million people worldwide are affected by Diabetes mellitus (DM); (2) Diabetes is going to be one of the top 10 causes of death by 2030; (3) diabetic disease results in a number of health complications, including diabetic nephropathy (DN), diabetic retinopathy, and diabetic neuropathy; (4) the prevalence of diabetic retinopathy may increase in the US from 7.7 million to 14.5 million in the next few decades; (5) 80% of patients with diabetics for 20 years or more may develop diabetic retinopathy; (5) diabetic retinopathy is the leading cause of adult blindness; (6) life-long painful injection/drug treatment is required to treat DM and its associated complications; (3) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM; (ii) a way to remove accumulation of lipids in different tissues, such as skeletal muscle, liver, eye and kidney, that improve insulin signalling and sensitivity; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, diabetes and its associated complications.
What is known?
Prof.Ingrid Fleming’s research team has recently shown that: (1) Soluble epoxide hydrolase enzyme (sEH) promotes pericyte loss; (2) sEH initiates breakdown of endothelial barrier function; (3) sEH is highly expressed in the retinas and vitreous humour of diabetic patients; (4) sEH enzyme makes 19,20-dihydroxydocosapentaenoic acid (Pro-inflammatory) from docosahexaenoic acid (Anti-inflammatory); (5) 19,20-dihydroxydocosapentaenoic acid disrupts the localization of cholesterol-binding proteins to the cell membrane; (6) 19,20-dihydroxydocosapentaenoic acid disrupts the association of presenilin1 with either N-cadherin or VE-cadherin; (7) 19,20-dihydroxydocosapentaenoic acid alters pericyte-endothelial cell interations and inter-endothelial cell junctions; (8) sEH is overexpressed in retinal muller glial cells, and promotes formation of abnormal vessels; (9) overexpression of sEH worsens the progression of diabetic retinopathy; (10) sEH inhibitor prevents: (a) pericyte loss; (b) vascular permeability; (c) inflammation of the retina; and (d) progression of diabetic retinopathy, suggesting that decreasing the expression of sEH in diabetic patients may attenuate the progression of diabetic retinopathy.
From research findings to Therapeutic opportunity:
This study suggests a natural product based therapy for Diabetic retinopathy.
This study suggests, for the first time, that D-3 Hydroxybutyrate (D3HB), by increasing the expression of its target genes, it may decrease the expression of Soluble epoxide hydrolase (sEH). Thereby, it may: (1) reduce the levels of toxic 19,20-dihydroxydocosapentaenoic acid; (2) increase pericyte viability; (3) strengthen endothelial barrier function;(4) prevent vascular permeability; (5) inhibit abnormal blood vessel formation; (6) improve Diabetic retinopathy-associated pathophysiologies; and (7) prevent vision loss (Fig.1).
Thus, pharmacological formulations encompassing “D-3 Hydroxybutyrate (D3HB) or its analogues, either alone or in combination with other drugs,” may be used in the treatment/prevention of Diabetic retinopathy.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by:
Dr L Boominathan Ph.D.
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
Undisclosed mechanistic information: How does D-3 Hydroxybutyrate (D3HB) decrease the expression of Soluble epoxide hydrolase (sEH) to prevent diabetic retinopathy?
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Citation: Boominathan, L., Molecular therapy for Diabetic retinopathy: D-3 Hydroxybutyrate (D3HB) inhibits Soluble epoxide hydrolase (sEH) expression, decreases toxic 19,20-dihydroxydocosapentaenoic acid levels, inhibits pericyte loss, vascular permeability, and inflammation of the eye and progression of diabetic retinopathy, via down regulation of its target gene, 11/February/2017, 12.33 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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