title: Increased basement membrane thickness, pericyte ghosts, and loss of retinal thickness and cells in dopamine beta hydroxylase knockout mice.
abstract: Diabetes can cause damage to sympathetic nerves, and we have previously shown that experimental sympathectomy can produce capillary abnormalities in the retina similar to those seen in early diabetes. We postulate that the diabetes-induced loss of the sympathetic system, and at least in part the sympathetic neurotransmitter norepinephrine (NE), contributes to the development of retinal vascular and neural abnormalities in diabetes. Thus, we predict that non-diabetic animals that lack NE will develop microvascular and neural changes that are similar to those that are characteristic of diabetic retinopathy. To test this, retinas from non-diabetic dopamine beta hydroxylase (Dbh, Dbh(-/-)) knockout mice and their littermate controls were assessed for diabetic-like capillary and neural changes at 5 months of age. Genetic deletion of Dbh resulted in a significant decrease in retinal thickness and number of cells in the retinal ganglion cell layer (central retinal region). In addition, the number of pericyte ghosts and the basement membrane of retinal capillaries were significantly increased in the Dbh(-/-) mice. These results provide evidence that loss of sympathetic neurotransmission may contribute to the microvascular and neural changes of diabetic retinopathy. Restoration of sympathetic neurotransmission may be a new target for therapeutic intervention to inhibit the early phases of diabetic retinopathy.
authors.affiliation: Departments of Ophthalmology and Anatomy and Neurobiology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA. jsteinl1@utmem.edu
authors.forename: Jena J
authors.initials: JJ
authors.lastname: Steinle
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.forename: Steven A
authors.initials: SA
authors.lastname: Thomas
authors.forename: Lisa S
authors.initials: LS
authors.lastname: McFadyen-Ketchum
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Smith
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000473:pathology*; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020286:Pericytes / Q000473:pathology*; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D012171:Retinal Vessels / Q000648:ultrastructure
chemical_list: D004299:Dopamine beta-Hydroxylase