Expression of the IGF system in normal and diabetic transgenic (mRen-2)27 rat eye.
OBJECTIVE
In the present study, a recently described model of diabetic eye disease was used to investigate the distribution of the insulin-like growth factor (IGF) system in the eyes of transgenic (mRen-2)27 rats (exhibiting hypertension and elevated serum and ocular renin levels) with streptozotocin-induced diabetes.


METHODS
Female transgenic (mRen-2)27 rats were randomized to receive either streptozotocin (diabetic) or citrate buffer (control). After 10 months, the rats were killed and the eyes fixed and embedded in paraffin. In situ hybridization (ISH) was used to document the cellular distribution of mRNAs for components of the IGF system (IGF-I, IGF-I receptor [IGFIR] and IGF binding proteins [IGFBP]1 to -6) in the eyes.


RESULTS
In nondiabetic rats, mRNA for IGFBP-1, -5, and -6; IGF-I; and IGFIR were detected in the retina. In addition, IGF-I mRNA was present in the cornea, IGFBP-1 mRNA was observed in the cornea and iris, and IGFBP-5 and -6 mRNAs were identified in the ciliary body, iris, and cornea. mRNAs for IGFBP-2, -3, and -4 were not found in the eyes. In diabetic rats, reduced levels of IGFBP-6 mRNA were detectable, whereas levels of IGFBP-5 mRNA were increased in the inner and outer retina, rods and cones, iris, cornea, and ciliary body. Other components of the IGF system in the eye were unchanged with diabetes.


CONCLUSIONS
In the diabetic (mRen-2)27 rat, IGFBP-6 is downregulated and IGFBP-5 is upregulated by induction of diabetes. Because these IGFBPs may respectively have IGF-enhancing and IGF-inhibitory effects, these findings suggest a possible net IGF-enhancing effect induced by diabetes, providing further evidence for a role of the IGF system in the development of diabetic retinopathy.
Bergman
Philip B
PB
Centre for Hormone Research, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia. philip.bergman@southernhealth.org.au
Moravski
Christina J
CJ
Edmondson
Stephanie R
SR
Russo
Vincenzo C
VC
Bach
Leon A
LA
Wilkinson-Berka
Jennifer L
JL
Werther
George A
GA
D000818:Animals; D030801:Animals, Genetically Modified; D002924:Ciliary Body / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007498:Iris / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D012083:Renin / Q000235:genetics; D012160:Retina / Q000378:metabolism
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; C473112:Ren2 protein, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D012083:Renin