Electroretinogram of Human, Monkey and Mouse

The electroretinogram (ERG) is a useful tool for objective, non-invasive assessment of retinal function both in the clinic and the laboratory. It is a mass electrical potential that represents the summed response of all the cells in the retina to a change in illumination. Recordings can be made in vivo under physiological or nearly physiological conditions using electrodes placed on the corneal surface. For standard recordings in the clinic, ERGs such as those illustrated in Figure 24.1 are recorded from alert subjects who are asked not to blink or to move their eyes. Anesthesia, selected for having minimal effects on retinal function, may be required for recordings from some very young human subjects, and is generally used for recordings in animals. The positive and negative waves of the ERG reflect the summed activity of overlapping positive and negative component potentials that originate from different stages of retinal processing. The choice of stimulus conditions and method of analysis will determine which of the various retinal cells and circuits are generating the response. Information about retinal function provided by the ERG is useful for diagnosing and characterizing retinal diseases, as well as for monitoring disease progression, and evaluating the effectiveness of therapeutic interventions. Much of the basic research on the origins, pathophysiology and treatment of retinal diseases that occur in humans is carried out in animal models. The ERG provides a simple objective approach for assessing retinal function in animals. In recent years it has been of particular benefit in studies of mouse (rat, and other species) models of retinal disease, and it has been valuable for evaluating the retinal drug toxicity. The ERG also has been useful for characterizing changes in retinal function that occur as a consequence of genetic alterations in mice and other models, which affect the transmission and processing of visual signals in the retina. This chapter provides information on retinal origins and interpretation of the ERG, with emphasis on advances in our understanding of the ERG that have occurred through pharmacological dissection studies in macaque monkeys whose retinas are similar to those of humans. The similarity of the waveforms of flash ERGs of humans and macaques can be seen in Figure 24.2. The chapter also will examine origins of the mouse ERG, and consider similarities and differences between mouse and primate ERG. Although the focus of this chapter is on primate and rodent retinas, it is important to note that the ERG is a valuable tool for assessing retinal function of all classes of vertebrates. This includes amphibians and fish in which classical studies of the retina were carried out (for a review, see Dowling) and in which current work continues to improve our understanding of retinal function under normal, genetically altered and pathological conditions. This chapter provides useful background information for interpreting the ERG, but does not provide a comprehensive review of the characteristics of ERGs associated with retinal disorders encountered in the clinic. Recent texts by Fishman et al, Heckenlively & Arden and Lam are recommended resources for learning more about clinical applications.