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ILAR Journal V40(2) 1999
Animal Models of Human Vision

Introduction
Richard C. Van Sluyters

The eye sends, as we saw, into the cell-and-fibre forest of the brain, throughout the waking day continual rhythmic streams of tiny, individually evanescent, electrical potentials. This throbbing streaming crowd of electrically shifting points in the spongework of the brain bears no obvious semblance in space-pattern, and even in temporal relation resembles but a little remotely the tiny two-dimensional upside-down picture of the outside world which the eyeball paints on the beginnings of its nerve-fibres to the brain. But that little picture sets up an electrical storm .... A shower of little electrical leaks conjures up for me, when I look at him approaching, my friend's face, and how distant he is from me they tell me. Taking their word for it, I go forward and my other senses confirm that he is there. (Sherrington 1940, p 128-129)

This lovely passage, written when the English physiologist Sir Charles Scott Sherrington was in his mid-eighties, elegantly captures the intricate beauty and compelling power of our visual sense. Most of what we learn and remember about the world is based on sight. The visual system is by far the most complex of our sensory systems. The two million axons in the optic nerves far exceed the total number of fibers in our other sensory nerves, including all the dorsal root fibers that enter the spinal cord. It is precisely because the sense of sight is so important in our daily lives that we value it so highly. A survey by the National Institutes of Health, National Eye Institute (NEI¹), and the Lions Club International revealed that among five potential disabilities (loss of eyesight, memory, hearing, speech, an arm, or a leg), Americans considered blindness as the worst personal disability.

The visual system is the focus of this issue of ILAR Journal, which is the latest in a series of issues focused on various research-oriented themes. Previous research themes have included "Models of Type I Diabetes--Parts One and Two" (35:1-2, 1993), "Advances in Gene Therapy" (36:3-4, 1994), "Perspectives on Xenotransplantation" (37:1, 1995), and "Animal Models of Aging Research" (38:3, 1997). The four papers in the current issue were contributed by some of the leading scientists in their areas. They present an overview of contemporary vision research and highlight the continuing importance of animal models in this field.

The paper by Cowell and others (1999) reviews research on bacterial infections of the cornea, the clear avascular tissue at the front of the globe that accounts for most of the eye's refractive power. According to the NEI, diseases and injury to the cornea are the leading cause of visits to eye specialists for medical care in the United States. Cowell and others describe the use of in vitro and in vivo methods to study infection of the cornea by Pseudomonas aeruginosa, a virulent bacterial pathogen commonly isolated from corneal ulcers. They note the alarming relation that has been demonstrated between this opportunistic pathogen and contact lens-associated ulcerative incidents, and they point out the continuing importance of animal models in studies of the origin and treatment of corneal infections.

Most blindness and visual disability in the United States are caused by diseases and disorders of the light-sensitive retina and the layer of blood vessels known as the choroid, which underlies the retina at the back of the eye. The retina contains the rod and cone photoreceptors and the complex network of neurons that process visual signals and relays them to the brain. A large proportion of retinal diseases is known to have a clear genetic basis; and, as the paper by Flannery (1999) points out, there are no effective therapies currently available for these progressive diseases. Flannery reviews the impact of transgenic techniques on the development of important new animal models for inherited retinal dystrophies. He describes ongoing efforts to develop viral-mediated gene therapies for retinal disorders and underscores the critical role that animal models are playing in this exciting area.

Epidemiological data from the NEI reveal that myopia, or nearsightedness, is found in 2% of preschoolers, 15% of high school graduates, and 25% of all Americans. About one half of all nearsightedness develops during the elementary school years, and the cost of myopia to our society is enormous--more than $1.5 billion per year in eyeglasses alone. The paper by Norton (1999) notes that despite all this, we know very little about why a particular child becomes myopic, what the risk factors are, and how the growth of the eye during childhood leads to myopia. His review of animal models of myopia describes current work directed toward discovering how visual experience controls the size of the eye (and hence its refractive state). Fish, chicks, kestrels, gray squirrels, rabbits, tree shrews, cats, marmosets, and nonhuman primates all have been used to increase our understanding of the role of the visual environment in the development of refractive error. Norton presents a model of the mechanism by which the eye may regulate its overall refractive status during growth. He notes that research in this field is in a very productive phase and predicts that the use of animal models is likely to continue or even accelerate.

The final vision-related paper by Newsome and Stein-Aviles (1999) surveys the use of nonhuman primates in studies of visually based cognition. They note that perhaps the greatest challenge facing natural scientists is the attempt to understand the neural processes that underlie perception, memory, learning, emotion, decision making, communication, and planning. Researchers in this field seek to link the activity of single neurons or clusters of neurons in the cerebral cortex to specific forms of behavior. Newsome and Stein-Aviles note that investigations of higher brain function are not possible using cell culture or computational modeling techniques. Limitations in the spatial and temporal resolution of even the most powerful human brain imaging techniques also restrict their usefulness, leaving the study of awake, behaving nonhuman primates as the most productive approach currently available for studying signal processing inside the brain. These authors review the results of exciting and innovative studies in which experimenters use micro-electrodes to monitor the activity of single cells while a highly trained monkey performs a complex behavioral task. They foresee steady progress toward unraveling the brain's innermost secrets and predict that eventually we will come to understand the linkage between abnormal information processing and mental disorders.

The editors of ILAR Journal thank these authors for providing our readers with this series of fascinating and informative papers on animal models of human vision. We hope you will find them as enjoyable as we have, and we look forward to providing you with future issues that are linked to specific research themes.

¹Abbreviation used in this paper: NEI, National Eye Institute.

References

Cowell BA, Wu C, Fleiszig SMJ. Use of an animal model in studies of bacterial corneal infection. ILAR J 40:43-50.

Flannery JG. Transgenic animal models for the study of inherited retinal dystrophies. ILAR J 40:51-58.

Newsome WT, Stein-Aviles JA. Nonhuman primate models of visually based cognition. ILAR J 40:78-91.

Sherrington Sir C. 1940. Man on His Nature. London, England: Cambridge University Press.

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