Strain-dependent increases in retinal inflammatory proteins and photoreceptor FGF-2 expression in streptozotocin-induced diabetic rats.
OBJECTIVE
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.
Kirwin
Stefanie J
SJ
Department of Biological Sciences, Allergan, Inc., 2525 Dupont Drive, Irvine, CA 92612, USA. kirwin_stefanie@allergan.com
Kanaly
Suzanne T
ST
Linke
Noelle A
NA
Edelman
Jeffrey L
JL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008297:Male; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012173:Retinitis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D016207:Cytokines; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2