Comparison of three strains of diabetic rats with respect to the rate at which retinopathy and tactile allodynia develop.
OBJECTIVE
We compared three rat strains to determine if different strains develop early-stage diabetic retinopathy or sensory neuropathy at different rates.


METHODS
Sprague Dawley, Lewis, and Wistar rats were made diabetic with streptozotocin. Diabetic and nondiabetic animals had retinal vascular pathology measured at eight months of diabetes. The number of cells in the retinal ganglion cell layer (GCL), retinal function (using electroretinography [ERG]), and retinal levels of inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2), and vascular endothelial growth factor (VEGF) were measured at four months of diabetes. Tactile allodynia was assessed in hind paws at two months of diabetes.


RESULTS
Diabetes of eight months' duration resulted in a significant increase in retinal degenerate capillaries and pericyte ghosts in Lewis and Wistar rats, but not in Sprague Dawley rats. A significant loss of cells in the GCL occurred only in diabetic Lewis rats, whereas Wistar and Sprague Dawley rats showed little change. Diabetes-induced iNOS and VEGF were statistically significant in all strains. Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley and Wistar strains. Lewis rats showed a similar trend, however, the results were not statistically significant. All strains tended to show diabetes-induced impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis strains had a significant reduction in latency. All strains showed significant tactile allodynia in peripheral nerves.


CONCLUSIONS
At the durations studied, Lewis rats showed accelerated loss of both retinal capillaries and ganglion cells in diabetes, whereas diabetic Wistar rats showed degeneration of the capillaries without significant neurodegeneration, and Sprague Dawley rats showed neither lesion. Identification of strains that develop retinal lesions at different rates should be of value in investigating the pathogenesis of retinopathy.
Kern
T S
TS
Case Western Reserve University, Center for Diabetes Research, Cleveland, OH 44106, USA. tsk@case.edu
Miller
C M
CM
Tang
J
J
Du
Y
Y
Ball
S L
SL
Berti-Matera
L
L
D000818:Animals; D002196:Capillaries / Q000473:pathology; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000150:complications* / Q000473:pathology*; D006941:Hyperesthesia / Q000150:complications* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D017933:Peripheral Nervous System / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000473:pathology
D018836:Inflammation Mediators
Am J Pathol. 2000 May;156(5):1733-9
10793084
Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3972-8
11053301
Nat Genet. 1999 Jan;21(1):76-83
9916795
FASEB J. 2003 Nov;17(14):2112-4
12958152
Diabetes. 1997 Nov;46(11):1829-39
9356033
J Comp Neurol. 1997 Jan 20;377(3):443-64
8989657
Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E763-74
12799319
J Clin Invest. 1998 Aug 15;102(4):783-91
9710447
Diabetes Nutr Metab. 2000 Apr;13(2):75-9
10898124
Diabetologia. 1995 Mar;38(3):269-73
7758871
Am J Physiol Renal Physiol. 2004 Sep;287(3):F347-52
15297276
Nat Genet. 2001 May;28(1):58-63
11326277
Diabetes. 1995 Jul;44(7):727-32
7789640
Am J Pathol. 2005 Jan;166(1):313-21
15632023
Nat Genet. 2002 Jul;31(3):235-6
12089518
FASEB J. 2002 Mar;16(3):438-40
11821258
Am J Ophthalmol. 2002 Mar;133(3):373-85
11860975
Semin Immunopathol. 2008 Apr;30(2):65-84
18340447
Exp Diabetes Res. 2007;2007:95103
18274606
Diabetes. 1997 Feb;46(2):287-91
9000706
Ophthalmic Genet. 2003 Mar;24(1):41-8
12660865
Diabetes. 1991 Feb;40(2):204-10
1991571
Br J Ophthalmol. 2002 Apr;86(4):363-5
11914197
Neurosci Lett. 2001 Feb 16;299(1-2):21-4
11166928
Neuropathology. 2002 Sep;22(3):161-70
12416555
Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1445-52
15790914
FASEB J. 2004 Sep;18(12):1450-2
15231732
J Diabetes Complications. 2005 Mar-Apr;19(2):70-3
15745835
Invest Ophthalmol Vis Sci. 2002 May;43(5):1595-603
11980879
FASEB J. 2004 Jul;18(10):1050-9
15226265
Curr Med Chem. 2003 Aug;10(15):1389-98
12871136
Diabetes. 1973 Aug;22(8):613-8
4724235
Diabetes. 2001 Aug;50(8):1938-42
11473058
Med Hypotheses. 2003 Apr;60(4):550-1
12615520
Diabetes. 2002 Dec;51(12):3499-504
12453906
Curr Eye Res. 1994 Dec;13(12):863-7
7720392
Diabetes. 2001 Jun;50(6):1432-9
11375345
Invest Ophthalmol Vis Sci. 2010 Apr;51(4):2158-64
20071676
Diabet Med. 2004 Dec;21(12):1325-33
15569136
J Neurosci Methods. 1994 Jul;53(1):55-63
7990513
Diabet Med. 2002 Nov;19(11):910-6
12421427
J Clin Invest. 1996 Jun 15;97(12):2883-90
8675702
Diabetes. 2002 Apr;51(4):1218-25
11916948
Diabetes. 1982 Mar;31(3):226-31
6818073
Kidney Int. 1992 Jul;42(1):106-14
1635340
Diabetologia. 1996 Nov;39(11):1313-7
8932997
Pain. 2001 Feb 1;90(1-2):75-82
11166972
Pain. 2002 Jun;97(3):203-212
12044617
Nat Med. 2003 Mar;9(3):294-9
12592403
J Physiol. 2008 Sep 15;586(18):4401-8
18565995
Eye (Lond). 2003 Apr;17(3):305-11
12724690
Diabetes Care. 2003 Aug;26(8):2410-5
12882871
Diabetes Res Clin Pract. 2003 Aug;61(2):133-6
12951282
Diabetes. 2007 Feb;56(2):373-9
17259381
Pain. 1996 Dec;68(2-3):293-9
9121817
Diabetes. 2007 Feb;56(2):337-45
17259377
Kidney Int. 1998 Dec;54(6):1999-2007
9853264
Diabet Med. 1995 Nov;12(11):997-1001
8582133
Diabetes. 1993 Jun;42(6):820-5
8495805
Nat Genet. 2001 May;28(1):42-5
11326273
Pharmacol Biochem Behav. 2000 Jan 1;65(1):141-4
10638647
Ophthalmologica. 2003 May-Jun;217(3):219-24
12660488
Diabetes Care. 1991 Jul;14(7):655-64
1914815
Diabetes Care. 1995 Jul;18(7):983-5
7555560
Ophthalmology. 1996 Nov;103(11):1820-8
8942877
Genetics. 2005 Feb;169(2):855-62
15371360
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11555-8
1763069
Curr Med Chem. 2003 Aug;10(15):1375-87
12871135
Carcinogenesis. 1988 Apr;9(4):625-7
2833368
Inflamm Res. 1997 Aug;46(8):299-305
9297574
Diabetes. 2004 Nov;53(11):2960-7
15504977
Diabetes. 2008 Oct;57(10):2801-8
18633115
Int Rev Neurobiol. 2002;50:205-28
12198811
Pharmacol Res. 2001 Aug;44(2):117-22
11516261
Lab Anim Sci. 1997 Aug;47(4):354-61
9306308
Semin Ophthalmol. 1999 Dec;14(4):240-8
10758225
J Clin Invest. 1997 Sep 1;100(5):1240-7
9276742
Diabetes. 2001 Jul;50(7):1636-42
11423486
Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4064-8
11095596
Diabetes. 2008 May;57(5):1387-93
18346986
Diabetes. 1992 Jul;41(7):879-85
1612203
Diabetologia. 2007 Sep;50(9):1987-1996
17583794