Journal article
Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus
Proceedings of the National Academy of Sciences of the United States of America, Vol.113(19), pp.E2655-E2664
05/10/2016
DOI: 10.1073/pnas.1522014113
PMCID: PMC4868487
PMID: 27114552
Abstract
Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.
Details
- Title: Subtitle
- Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus
- Creators
- Elliott H Sohn - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242; michael-abramoff@uiowa.eduHille W van Dijk - Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; michael-abramoff@uiowa.eduChunhua Jiao - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242Pauline H B Kok - Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsWoojin Jeong - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242Nazli Demirkaya - Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsAllison Garmager - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242Ferdinand Wit - Department of Global Health, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsMurat Kucukevcilioglu - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242Mirjam E J van Velthoven - Oogziekenhuis Rotterdam, 3011 BH Rotterdam, The NetherlandsJ Hans DeVries - Department of Endocrinology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsRobert F Mullins - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242Markus H Kuehn - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242Reinier Otto Schlingemann - Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsMilan Sonka - Iowa Institute for Biomedical Imaging, University of Iowa, Iowa City, IA 52242; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA 52242Frank D Verbraak - Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsMichael David Abràmoff - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242; Iowa Institute for Biomedical Imaging, University of Iowa, Iowa City, IA 52242; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA 52242; Iowa City VA Health Care System, Iowa City, IA 52246; Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242 michael-abramoff@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences of the United States of America, Vol.113(19), pp.E2655-E2664
- DOI
- 10.1073/pnas.1522014113
- PMID
- 27114552
- PMCID
- PMC4868487
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- R01 EB004640 / NIBIB NIH HHS R01 EY017066 / NEI NIH HHS I01 RX001163 / RRD VA R01 EY019112 / NEI NIH HHS R01 EY016379 / NEI NIH HHS R01 EY018853 / NEI NIH HHS I01 CX000119 / CSRD VA
- Language
- English
- Date published
- 05/10/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Radiation Oncology; Injury Prevention Research Center; Ophthalmology and Visual Sciences
- Record Identifier
- 9983806396102771
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