PMID- 28548649 OWN - NLM STAT- MEDLINE DCOM- 20180223 LR - 20181113 IS - 1476-5454 (Electronic) IS - 0950-222X (Print) IS - 0950-222X (Linking) VI - 31 IP - 10 DP - 2017 Oct TI - Aqueous humor endothelin-1 and total retinal blood flow in patients with non-proliferative diabetic retinopathy. PG - 1443-1450 LID - 10.1038/eye.2017.74 [doi] AB - PurposeThe purpose of this study was to determine the association between aqueous ET-1 levels and total retinal blood flow (TRBF) in patients with non-insulin-dependent type 2 diabetes mellitus (T2DM) and early non-proliferative diabetic retinopathy (NPDR).Patients and methodsA total of 15 age-matched controls and 15 T2DM patients with NPDR were recruited into the study. Aqueous humor (~80-120 mul) was collected before cataract surgery to measure the levels of ET-1 using suspension multiplex array technology. Four weeks post surgery, six images were acquired to assess TRBF using the prototype RTVue Doppler FD-OCT (Optovue, Inc., Fremont, CA, USA) with a double circular scan protocol. At the same visit, forearm blood was collected to determine plasma glycosylated hemoglobin (A1c) levels.ResultsAqueous ET-1 was significantly elevated in the NPDR group compared with the control group (3.5+/-1.8 vs 2.2+/-0.8, P=0.02). TRBF was found to be significantly reduced in the NPDR group compared with the control group (34.5+/-9.1 vs 44.1+/-4.6 mul/min, P=0.002). TRBF and aqueous ET-1 were not correlated within the NPDR group (r=-0.24, P=0.22). In a multivariate analysis, high A1c was associated with reduced TRBF and aqueous ET-1 levels across control and NPDR groups (P<0.01).ConclusionAqueous ET-1 levels were increased while TRBF was reduced in patients with NPDR compared with the control group. Although not directly associated, the vasoconstrictory effects of ET-1 are consistent with a reduced TRBF observed in early DR. ET-1 dysregulation may contribute to a reduction in retinal blood flow during early DR. FAU - Khuu, L-A AU - Khuu LA AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. AD - Vision Science and Ophthalmology, Toronto Western Hospital, Toronto, ON, Canada. FAU - Tayyari, F AU - Tayyari F AD - School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada. FAU - Sivak, J M AU - Sivak JM AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. FAU - Flanagan, J G AU - Flanagan JG AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. AD - Vision Science and Ophthalmology, Toronto Western Hospital, Toronto, ON, Canada. AD - School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada. FAU - Singer, S AU - Singer S AD - Vision Science and Ophthalmology, Toronto Western Hospital, Toronto, ON, Canada. FAU - Brent, M H AU - Brent MH AD - Vision Science and Ophthalmology, Toronto Western Hospital, Toronto, ON, Canada. FAU - Huang, D AU - Huang D AD - Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA. FAU - Tan, O AU - Tan O AD - Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA. FAU - Hudson, C AU - Hudson C AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. AD - Vision Science and Ophthalmology, Toronto Western Hospital, Toronto, ON, Canada. AD - School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada. LA - eng GR - DP3 DK104397/DK/NIDDK NIH HHS/United States GR - R01 EY023285/EY/NEI NIH HHS/United States GR - UL1 TR000128/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20170526 PL - England TA - Eye (Lond) JT - Eye (London, England) JID - 8703986 RN - 0 (Biomarkers) RN - 0 (Endothelin-1) SB - IM MH - Aged MH - Aqueous Humor/*metabolism MH - Biomarkers/metabolism MH - Diabetes Mellitus, Type 2/*complications MH - Diabetic Retinopathy/etiology/metabolism/*physiopathology MH - Endothelin-1/*metabolism MH - Female MH - Humans MH - Male MH - Regional Blood Flow/*physiology MH - Retinal Vessels/diagnostic imaging/*physiopathology MH - Tomography, Optical Coherence/methods PMC - PMC5639192 COIS- DH and OT have significant financial interest in Optovue, a company that may have a commercial interest in the results of this research and technology. CH received support in terms of loaned equipment and funding for research. These potential conflicts of interest have been reviewed and managed by the Research Ethics Board of the University Health Network, Toronto and by Oregon Health & Science University. The remaining authors declared no conflict of interest. EDAT- 2017/05/27 06:00 MHDA- 2018/02/24 06:00 PMCR- 2018/10/01 CRDT- 2017/05/27 06:00 PHST- 2015/07/19 00:00 [received] PHST- 2017/03/14 00:00 [accepted] PHST- 2017/05/27 06:00 [pubmed] PHST- 2018/02/24 06:00 [medline] PHST- 2017/05/27 06:00 [entrez] PHST- 2018/10/01 00:00 [pmc-release] AID - eye201774 [pii] AID - 10.1038/eye.2017.74 [doi] PST - ppublish SO - Eye (Lond). 2017 Oct;31(10):1443-1450. doi: 10.1038/eye.2017.74. Epub 2017 May 26.