Expression of Macrophage Colony-Stimulating Factor (M-CSF) and Its Receptor in Streptozotocin-Induced Diabetic Rats

Purpose: 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.