Expression of macrophage colony-stimulating factor (M-CSF) and its receptor in streptozotocin-induced diabetic rats.
OBJECTIVE
To demonstrate the expression and location of macrophage colony-stimulating factor (M-CSF) and its receptor (CSF-1R) in the retinas of diabetic rats, as well as in vitreous human proliferative diabetic retinopathy (PDR).


METHODS
The retinas of streptozotocin-induced diabetic rat were studied. Real-time PCR was applied to evaluate M-CSF and its receptor CSF-1R mRNA expression in the retinas. The protein levels of M-CSF and CSF-1R were evaluated by Western blot analysis. Cellular sources of M-CSF and CSF-1R were determined by double-immunofluorescence staining. M-CSF levels in vitreous samples from patients with PDR were measured by ELISA.


RESULTS
M-CSF and CSF-1R mRNA were upregulated in the retinas as early as two weeks after the onset of diabetes and increased over time. A similar pattern was observed for M-CSF/CSF-1R protein expression levels. Double-immunofluorescence staining revealed that increased M-CSF immunoreactivity occurred mainly in the nerve fiber layer in diabetic retinas, co-localizing with glial fibrillary acidic protein. Increased CSF-1R immunoreactivity was observed in OX-42-labeled microglia and ganglion cells in the ganglion cell layer. The vitreous level of M-CSF was elevated in patients with PDR compared to control subjects.


CONCLUSIONS
The early upregulation of MCSF/CSF-1R signaling may be an important regulatory pathway among neurons, microglia, and glia in diabetic retinopathy.
Liu
Wei
W
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
Xu
Ge-zhi
GZ
Jiang
Chun-hui
CH
Da
Cui-di
CD
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D012160:Retina / Q000201:enzymology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin / Q000633:toxicity
D013311:Streptozocin; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor