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Sources of PDGF expression in murine retina and the effect of short-term diabetes.

Authors: Cox, OT  Simpson, DA  Stitt, AW  Gardiner, TA 
Citation: Cox OT, etal., Mol Vis. 2003 Dec 10;9:665-72.
Pubmed: (View Article at PubMed) PMID:14685146

PURPOSE: Progressive dysfunction and death of vascular smooth muscle cells and pericytes is a pathophysiological hallmark of diabetic retinopathy, although the underlying mechanisms behind this process remain ill-defined. The multifunctional peptide platelet-derived growth factor (PDGF) is known to act as an important survival factor for both of these vascular cell-types at times of physiological stress. The retinal cell source(s) of PDGF remain unknown. It is important to understand how diabetes alters expression of this important growth factor. METHODS: Streptozotocin-diabetes was established in C57 mice. Following 8 weeks of sustained diabetes, the eyes were enucleated and in situ hybridization was used to localize expression of PDGF-A and PDGF-B chains in retina from both diabetic and non-diabetic controls. mRNA levels for both forms of PDGF, and their cognate PDGF-alpha and PDGF-beta receptors, were also quantified using real-time PCR. RESULTS: In situ hybridization demonstrated that PDGF-A and PDGF-B were predominantly expressed by the retinal ganglion cells/nerve fibre layer in both normal and diabetic mice, and this localization pattern did not alter in diabetes. PDGF-A receptor was expressed exclusively in the ganglion cell layer of the retina while PDGF-B receptor was mostly localized to the Muller cell end-feet at the internal limiting membrane with lesser immunoreactivity in the ganglion cells, inner plexiform layer, and inner nuclear layer. PDGF-A and PDGF-alpha receptor mRNA expression levels remained unaltered between treatment groups, although retinal immunolocalization patterns between both receptors was distinct. However, there was a significant decrease of PDGF-B mRNA levels in diabetic retina when compared to non-diabetic controls (p<0.001), although there was no significant difference in PDGF-alpha receptor(insert space) expression. CONCLUSIONS: Previous studies have shown PDGF expression in a range of cell-types during retinal development, but these results confirm ganglion cells as the principal PDGF source in mature retina. It may be significant that diabetes can reduce PDGF-B mRNA expression since this may have serious implications for vascular survival during diabetic retinopathy progression.


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CRRD Object Information
CRRD ID: 2311648
Created: 2009-07-28
Species: All species
Last Modified: 2009-07-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.