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5 In Vivo Models of Diabetic
Retinopathy
Timothy S. Kern
CONTENTS
WHAT DEFINES A GOOD ANIMAL MODEL OF DIABETIC
RETINOPATHY?
DIABETIC PRIMATES
DIABETIC DOGS
DIABETIC CATS
DIABETIC RATS
DIABETIC MICE
OTHER RODENTS
NONDIABETIC MODELS THAT DEVELOP ASPECTS
OF DIABETIC-LIKE RETINOPATHY
AREN’T THERE ANY “GOOD” MODELS OF DIABETIC
RETINOPATHY?
SUMMARY
REFERENCES
ABSTRACT
Animal models are being used by numerous investigators to study the pathogenesis of diabetic retinopathy. Each of the different animal models has advantages and disadvantages that should be kept in mind when selecting which model to use. This chapter will summarize the histopathology of animal models of diabetic retinopathy and will address four important topics for each model (type of diabetes, histopathology and rate of development of retinopathy, therapies or gene modifications studied in this model, and advantages and disadvantages of the model). Each of the diabetic models studied to date reproduces the capillary degeneration that characterizes the early stages of the retinopathy, but neurodegeneration has been studied only in diabetic rodents. Although none of the available models has been found to reliably develop preretinal neovascularization to date, this deficiency could be due to insufficient durations of diabetes (resulting in insufficient obliteration of retinal capillaries) rather than an intrinsic difference between humans and animal models.
From: Contemporary Diabetes: Diabetic Retinopathy
Edited by: E. Duh © Humana Press, Totowa, NJ
137
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Kern |
Key Words: Diabetic retinopathy; animal models; retina; pathogenesis.
The mechanisms leading to the development of diabetic retinopathy remain under investigation. Animal models of diabetic retinopathy remain a critical part of our efforts to understand the pathogenesis of the process and to identify promising ways to inhibit the retinal disease. This chapter will summarize the histopathology of animal models of diabetic retinopathy. For each animal model, we will address four pertinent questions that are relevant to the use of different species as a model of diabetic retinopathy (type of diabetes, histopathology and rate of development of retinopathy, therapies or gene modifications studied in this model, and advantages and disadvantages of the model).
WHAT DEFINES A GOOD ANIMAL MODEL
OF DIABETIC RETINOPATHY?
The value of any animal model depends in large part on how well the model reproduces lesions of the human disease. There have been some who said that there were no “good” or “appropriate” animal models of diabetic retinopathy, because available models have not been found to progress to the advanced lesions of the retinopathy. However, as desirable as that would be, is it necessary for each animal model to develop the full spectrum of lesions that characterize diabetic retinopathy? What is the value of models that develop the early stages of the retinopathy, but might not develop the more advanced lesions? These and other questions will be examined after summarizing the most utilized animal models.
Table 1 summarizes the types of lesions of retinopathy in diabetic humans and diabetic animals, and an approximate duration when the nonproliferative changes begin to
Table 1
Types of Lesions of Retinopathy in Diabetic Humans and Diabetic Animals
|
Human |
Primate |
Dog |
Cat |
Rat |
Mouse |
Pathology apparent |
7 + years |
7 + years |
3 + years |
4 + years |
½ + years |
½ + years |
|
|
|
|
|
|
|
Background |
|
|
|
|
|
|
Microaneurysms |
+ |
+ |
+ |
+ |
± |
0 |
Degenerate capillaries |
+ |
+ |
+ |
+ |
+ |
+ |
Pericyte loss |
+ |
+ |
+ |
+ |
+ |
+ |
IRMA |
+ |
+ |
+ |
+ |
0 |
0 |
Hemorrhages |
+ |
? |
+ |
+ |
0 |
0 |
BM thickening |
+ |
+ |
+ |
+ |
+ |
+ |
Neurodegeneration |
+ |
? |
? |
? |
+ |
± |
Retinal edema |
+ |
+ |
+ |
? |
? |
? |
Neovascularization |
|
|
|
|
|
|
Intraretinal |
+ |
? |
+ |
? |
? |
? |
Preretinal |
+ |
0 |
0 |
0 |
± |
0 |
Adapted with permission from Springer (156)