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Originally published In Press as doi:10.1167/iovs.09-3474 on May 27, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:5396-5404.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.09-3474
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Strain-Dependent Increases in Retinal Inflammatory Proteins and Photoreceptor FGF-2 Expression in Streptozotocin-Induced Diabetic Rats

Stefanie J. Kirwin,1 Suzanne T. Kanaly,2 Noelle A. Linke,2 and Jeffrey L. Edelman1

From the Departments of 1Biological Sciences and 2Pathology, Allergan, Inc., Irvine, California.

Corresponding author: Stefanie J. Kirwin, Allergan, Inc., Biological Science, 2525 Dupont Drive, Irvine, CA 92612; kirwin_stefanie{at}allergan.com.

Purpose. Inflammation is thought to play a role in disease progression and vision loss in diabetic retinopathy (DR). However, the level of inflammation and the role of cytokines and growth factors in the early stages of this disease are poorly understood. Streptozotocin (STZ)-induced hyperglycemia in rats is widely used as a model of diabetic retinopathy, and therefore this model was used to better define the inflammatory response and the impact of the genetic background.

Methods. The expression of a panel of 57 inflammatory proteins and growth factors in the retina of three rat strains was compared by using a highly sensitive flow cytometry–based assay. Hyperglycemia was induced in Brown Norway (BN), Long-Evans (LE), and Sprague-Dawley (SD) rats, and protein expression in the retina was measured 4 weeks and 3 months later.

Results. The data revealed a subtle, but reproducible, inflammatory response in the retina of SD, but not in those of BN or LE, rats. Upregulation of fibroblast growth factor (FGF)-2 in the photoreceptor nuclear layer coincided with the inflammatory response in SD rats and may constitute a neuroprotective mechanism. Reduced expression of genes involved in the phototransduction pathway indicates altered photoreceptor function.

Conclusions. Taken together, these data show that inflammatory changes in the diabetic rat retina are highly strain dependent, and SD rats exhibit low-level inflammation similar to that observed in diabetic patients. Therefore, SD rats may be a good model for the study of early inflammatory changes in human diabetic retinopathy.






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