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March 1995, Vol 113, No. 3 >
ARTICLE | March 1995

The Galactosemic Dog: Title and subTitle BreakA Valid Model for Both Early and Late Stages of Diabetic Retinopathy FREE

Robert N. Frank, MD
Arch Ophthalmol. 1995;113(3):275-276. doi:10.1001/archopht.1995.01100030029016
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AN ACCURATE animal model of a human disease can help us to understand the pathogenesis of the disease, to study its cellular and molecular mechanisms of progression, and to test new therapeutic approaches before they are ready for evaluation in human subjects. The model of diabetic retinopathy in the long-term galactosemic dog, introduced by Engerman and Kern1 in 1984, is one of the best animal models now available in ophthalmic research. After 3 to 5 years on a diet containing 30% galactose, these animals accurately reproduce the lesions of early diabetic retinopathy in humans, and they do so following chronic elevation of an aldohexose that is structurally similar to glucose but does not enter into many of the biochemical pathways by which glucose is metabolized. In this issue of the Archives, Engerman and Kern2 and Kador et al3 report important new findings using this model that appear

REFERENCES

1 +
Engerman RL, Kern TS.  Experimental galactosemia produces diabetic-like retinopathy . Diabetes . 1984;;33:97-100.
2 +
Engerman RL, Kern TS.  Retinopathy in galactosemic dogs continues to progress after cessation of galactosemia . Arch Ophthalmol . 1994;;113:355-358.
3 +
Kador PF, Takahashi Y, Wyman M, Ferris F III.  Diabeteslike proliferative retinal changes in galactose-fed dogs . Arch Ophthalmol 1994;;113:352-354.
4 +
Patz A, Maumenee AE.  Studies on diabetic retinopathy, I: retinopathy in a dog with spontaneous diabetes mellitus . Am J Ophthalmol . 1962;;54:532-541.
5 +
Hausler HR, Sibay TM, Campbell J.  Retinopathy in a dog following diabetes induced by growth hormone . Diabetes . 1964;;13:122-126.
6 +
Engerman RL, Bloodworth JMB Jr.  Experimental diabetic retinopathy in dogs . Arch Ophthalmol . 1965;;73:205-210.
7 +
Engerman RL, Bloodworth JMB Jr, Nelson S.  Relationship of microvascular disease in diabetes to metabolic control . Diabetes . 1977;;26:760-769.
8 +
Diabetes Control and Complications Trial (DCCT) Research Group.  The effect of intensive treatment of diabetes on the development of long-term complications in insulin-dependent diabetes mellitus . N Engl J Med . 1993;;329:977-986.
9 +
Engerman RL, Kern TS.  Progression of incipient diabetic retinopathy during good glycemic control . Diabetes . 1984;;33:97-100.
10 +
Kroc Collaborative Study Group.  Blood glucose control and the evolution of diabetic retinopathy and albuminuria . N Engl J Med . 1984;;311:365-372.
11 +
Lauritzen T, Frost-Larsen K, Larsen HW, et al.  Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy . Diabetes . 1985;;34( (suppl 3) ):74-79.
12 +
Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, et al.  Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study . BMJ . 1985;;290:811-815.
13 +
Kador PF, Akagi Y, Terubayashi H, Wyman M, Kinoshita JH.  Prevention of pericyte ghost formation in retinal capillaries of galactose-fed dogs by aldose reductase inhibitors . Arch Ophthalmol . 1988;;106:1099-1102.
14 +
Kador PF, Akagi Y, Takahashi Y, Ikebe H, Wyman M, Kinoshita JH.  Prevention of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by aldose reductase inhibitors . Arch Ophthalmol . 1990;;108:1295-1301.
15 +
Engerman RL, Kern TS.  Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs . Diabetes . 1993;;42:820-825.
16 +
Robison WG Jr.  Aldose reductase inhibition and retinopathy . Diabetes . 1994;;43:337-338.
17 +
Engerman RL, Kern TS.  Response to Robison . Diabetes . 1994;;43:338-339.
18 +
Sorbinil Retinopathy Trial Research Group.  A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy . Arch Ophthalmol . 1990;;108:1234-1244.
19 +
Frank RN.  Aldose reductase inhibition . Arch Ophthalmol . 1990;;108:1229-1231.
20 +
Das A, Frank, RN, Zhang NL, Samadani E.  Increases in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening . Exp Eye Res . 1990;;50:269-280.
21 +
Patz A, Eastham A, Higgenbotham DH, Kleh T.  Oxygen studies in retrolental fibroplasia, II . Am J Ophthalmol . 1953;;36:1511-1522.
22 +
Patz A.  Studies on retinal neovascularization: the Friedenwald Lecture . Invest Ophthalmol Vis Sci . 1980;;19:1133-1138.
23 +
Shabo AL, Maxwell DS.  Insulin-induced immunogenic retinopathy resembling the retinitis proliferans of diabetes . Trans Am Acad Ophthalmol Otolaryngol . 1976;;81:OP-497-OP-508.
24 +
Shabo AL, Maxwell DS.  Experimental immunogenic proliferative retinopathy in monkeys . Am J Ophthalmol . 1977;;83:471-480.
25 +
Frank RN, Mancini MA.  Presumed retinovitreal neovascularization in dystrophic retinas of spontaneously hypertensive rats . Invest Ophthalmol Vis Sci . 1986;;27:346-355.
26 +
Weber ML, Mancini MA, Frank RN.  Retinovitreal neovascularization in the Royal College of Surgeons rat . Curr Eye Res . 1989;;8:61-74.
27 +
Murata T, Ishibashi T, Inomata H.  Experimental rat model of neovascularization arising from the optic disc . Ophthalmic Res . 1993;;25:157-161.
28 +
Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL.  The Wisconsin Epidemiologic Study of Diabetic Retinopathy, II . Arch Ophthalmol . 1984;;102:520-526.

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1 +
Engerman RL, Kern TS.  Experimental galactosemia produces diabetic-like retinopathy . Diabetes . 1984;;33:97-100.
2 +
Engerman RL, Kern TS.  Retinopathy in galactosemic dogs continues to progress after cessation of galactosemia . Arch Ophthalmol . 1994;;113:355-358.
3 +
Kador PF, Takahashi Y, Wyman M, Ferris F III.  Diabeteslike proliferative retinal changes in galactose-fed dogs . Arch Ophthalmol 1994;;113:352-354.
4 +
Patz A, Maumenee AE.  Studies on diabetic retinopathy, I: retinopathy in a dog with spontaneous diabetes mellitus . Am J Ophthalmol . 1962;;54:532-541.
5 +
Hausler HR, Sibay TM, Campbell J.  Retinopathy in a dog following diabetes induced by growth hormone . Diabetes . 1964;;13:122-126.
6 +
Engerman RL, Bloodworth JMB Jr.  Experimental diabetic retinopathy in dogs . Arch Ophthalmol . 1965;;73:205-210.
7 +
Engerman RL, Bloodworth JMB Jr, Nelson S.  Relationship of microvascular disease in diabetes to metabolic control . Diabetes . 1977;;26:760-769.
8 +
Diabetes Control and Complications Trial (DCCT) Research Group.  The effect of intensive treatment of diabetes on the development of long-term complications in insulin-dependent diabetes mellitus . N Engl J Med . 1993;;329:977-986.
9 +
Engerman RL, Kern TS.  Progression of incipient diabetic retinopathy during good glycemic control . Diabetes . 1984;;33:97-100.
10 +
Kroc Collaborative Study Group.  Blood glucose control and the evolution of diabetic retinopathy and albuminuria . N Engl J Med . 1984;;311:365-372.
11 +
Lauritzen T, Frost-Larsen K, Larsen HW, et al.  Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy . Diabetes . 1985;;34( (suppl 3) ):74-79.
12 +
Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, et al.  Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study . BMJ . 1985;;290:811-815.
13 +
Kador PF, Akagi Y, Terubayashi H, Wyman M, Kinoshita JH.  Prevention of pericyte ghost formation in retinal capillaries of galactose-fed dogs by aldose reductase inhibitors . Arch Ophthalmol . 1988;;106:1099-1102.
14 +
Kador PF, Akagi Y, Takahashi Y, Ikebe H, Wyman M, Kinoshita JH.  Prevention of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by aldose reductase inhibitors . Arch Ophthalmol . 1990;;108:1295-1301.
15 +
Engerman RL, Kern TS.  Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs . Diabetes . 1993;;42:820-825.
16 +
Robison WG Jr.  Aldose reductase inhibition and retinopathy . Diabetes . 1994;;43:337-338.
17 +
Engerman RL, Kern TS.  Response to Robison . Diabetes . 1994;;43:338-339.
18 +
Sorbinil Retinopathy Trial Research Group.  A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy . Arch Ophthalmol . 1990;;108:1234-1244.
19 +
Frank RN.  Aldose reductase inhibition . Arch Ophthalmol . 1990;;108:1229-1231.
20 +
Das A, Frank, RN, Zhang NL, Samadani E.  Increases in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening . Exp Eye Res . 1990;;50:269-280.
21 +
Patz A, Eastham A, Higgenbotham DH, Kleh T.  Oxygen studies in retrolental fibroplasia, II . Am J Ophthalmol . 1953;;36:1511-1522.
22 +
Patz A.  Studies on retinal neovascularization: the Friedenwald Lecture . Invest Ophthalmol Vis Sci . 1980;;19:1133-1138.
23 +
Shabo AL, Maxwell DS.  Insulin-induced immunogenic retinopathy resembling the retinitis proliferans of diabetes . Trans Am Acad Ophthalmol Otolaryngol . 1976;;81:OP-497-OP-508.
24 +
Shabo AL, Maxwell DS.  Experimental immunogenic proliferative retinopathy in monkeys . Am J Ophthalmol . 1977;;83:471-480.
25 +
Frank RN, Mancini MA.  Presumed retinovitreal neovascularization in dystrophic retinas of spontaneously hypertensive rats . Invest Ophthalmol Vis Sci . 1986;;27:346-355.
26 +
Weber ML, Mancini MA, Frank RN.  Retinovitreal neovascularization in the Royal College of Surgeons rat . Curr Eye Res . 1989;;8:61-74.
27 +
Murata T, Ishibashi T, Inomata H.  Experimental rat model of neovascularization arising from the optic disc . Ophthalmic Res . 1993;;25:157-161.
28 +
Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL.  The Wisconsin Epidemiologic Study of Diabetic Retinopathy, II . Arch Ophthalmol . 1984;;102:520-526.

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