Sympathetic innervation regulates basement membrane thickening and pericyte number in rat retina.
OBJECTIVE
To determine whether loss of sympathetic innervation alters basement membrane thickness and pericyte loss.


METHODS
Sympathetic innervation to the eye was destroyed by surgical removal of the right superior cervical ganglion in rats. Basement membrane changes were assessed by real-time PCR and electron microscopy. The number of pericytes was measured by immunofluorescent staining for NG2 proteoglycan. Steady-state mRNA levels were also evaluated for platelet-derived growth factor-BB (PDGF-BB).


RESULTS
Loss of sympathetic innervation caused a significant increase in steady state mRNA levels of fibronectin and a 15% increase in laminin-beta 1 mRNA 3 weeks after surgical sympathectomy. Protein expression also increased at this point. In addition, capillary basement membrane thickness increased significantly. NG2 proteoglycan staining decreased significantly in pericytes in the sympathectomized rat retina. Steady state mRNA for PDGF-BB decreased significantly 6 weeks after surgery.


CONCLUSIONS
Sympathetic nerves may be compromised in diabetes, and these findings suggest that they may regulate some complications of diabetic retinopathy. Gene expression levels of fibronectin and laminin-beta 1 changed between 1 and 3 weeks. These data are supported by electron microscopy, which showed the increase in basement membrane thickness in vivo. Loss of sympathetic innervation to the eye also caused a decrease in the number of pericytes. Steady state mRNA expression of PDGF-BB was reduced, suggesting a mechanism for the loss of pericytes in the sympathectomized retina. Overall, these results suggest that sympathetic nerve alterations may function in some complications observed in diabetic retinopathy, and this may be a suitable model to investigate therapies for this disorder.
Wiley
Luke A
LA
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901, USA.
Rupp
Gerald R
GR
Steinle
Jena J
JJ
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure*; D000077214:Becaplermin; D002452:Cell Count; D003930:Diabetic Retinopathy / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000235:genetics; D015171:Ganglionectomy; D005786:Gene Expression Regulation; D007797:Laminin / Q000235:genetics; D020286:Pericytes / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017783:Superior Cervical Ganglion / Q000502:physiology*; D013997:Time Factors
D005353:Fibronectins; C478221:LAMB1 protein, human; D007797:Laminin; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin