Braunger, Barbara M. and Leimbeck, Sarah V. and Schlecht, Anja and Volz, Cornelia and Jaegle, Herbert and Tamm, Ernst R. (2015) Deletion of Ocular Transforming Growth Factor beta Signaling Mimics Essential Characteristics of Diabetic Retinopathy. AMERICAN JOURNAL OF PATHOLOGY, 185 (6). pp. 1749-1768. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)Abstract
Diabetic retinopathy, a major cause of blindness, is characterized by a distinct phenotype. The molecular causes of the phenotype are not sufficiently clear. Here, we report that deletion of transforming growth factor beta signaling in the retinal microenvironment of newborn mice induces changes that largely mimic the phenotype of nonproliferative and proliferative diabetic retinopathy in humans. Lack of transforming growth factor beta signaling leads to the formation of abundant microaneurysms, leaky capillaries, and retinal hemorrhages. Retinal capillaries are not covered by differentiated pericytes, but by a coat of vascular smooth muscle-like cells and a thickened basal lamina. Reactive microglia is found in close association with retinal capillaries. In older animals, loss of endothelial cells and the formation of ghost vessels are observed, findings that correlate with the induction of angiogenic molecules and the accumulation of retinal hypoxia-inducible factor 1 alpha, indicating hypoxia. Consequently, retinal and vitreal neovascularization occurs, a scenario that leads to retinal detachment, vitreal hemorrhages, neuronal apoptosis, and impairment of sensory function. We conclude that transforming growth factor beta signaling is required for the differentiation of retinal pericytes during vascular development of the retina. Lack of differentiated pericytes initiates a scenario of structural and functional changes in the retina that mimics those of diabetic retinopathy strongly indicating a common mechanism.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROGRAMMED CELL-DEATH; SMOOTH-MUSCLE-CELLS; RETINAL VASCULAR PATTERNS; BLOOD-BRAIN-BARRIER; TGF-BETA; ENDOTHELIAL-CELLS; NEURAL CREST; CONDITIONAL INACTIVATION; DEFICIENT MICE; MAMMALIAN EYE; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2019 07:23 |
| Last Modified: | 15 Jul 2019 07:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5419 |
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