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Cone Pigments and Vision in the Mouse
Gerald H. Jacobs
CONTENTS
INTRODUCTION
PREVALENCE AND SPATIAL DISTRIBUTION OF MOUSE CONES
MOUSE CONE PIGMENTS
CONE SIGNAL PATHWAYS IN THE MOUSE RETINA
CONE-BASED VISION IN MICE
ALTERATIONS IN MOUSE VISION CONSEQUENT TO GENETIC MANIPULATIONS
MOUSE AND HUMAN CONE VISION
REFERENCES
INTRODUCTION
The house mouse (Mus musculus) originated in the northern Indian subcontinent approximately 1 million years ago [1]. More than 450 strains of mice have been derived from M. musculus stock for laboratory research [2], and in recent years various versions of this species have become the targets of choice for retinal research. This work generally professes the dual goals of illuminating basic retinal biology and of providing models for study of human retinal diseases. This chapter provides a context for evaluating those cases for which interest is focused on cone-based vision by examining what has been learned about the relationships between mouse cone photopigments and vision.
PREVALENCE AND SPATIAL DISTRIBUTION OF MOUSE CONES
All mammalian retinas contain a mixture of rods and cones, with the relative representation and the topographical distributions of the two receptor types varying enormously across the order [3, 4]. Although the early literature contains contradictory claims about the very presence of cones in the mouse, in 1979 Carter-Dawson and LaVail [5] showed that mouse cones could be differentiated from rods by applying several structural criteria (principally, location of the photoreceptor cell bodies in the outer nuclear layer, heterochromatin staining patterns, and morphology of the inner segments). Based on sample
From: Ophthalmology Research: Visual Transduction and Non-Visual Light Perception
Edited by: J. Tombran-Tink and C. J. Barnstable © Humana Press, Totowa, NJ
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counts made at three retinal locations, they concluded that cones constitute about 3% of the total mouse photoreceptors. More recently, peanut agglutinin (PNA) lectin binding has been widely employed as a marker to label mammalian cone photoreceptors [6]. Cone counts made using PNA labeling indicate that on average there are some 180,000– 190,000 cones in the retinas of C57/BL6 mice [7, 8].
As is the case for many other rodent retinas, there are only modest regional variations in cone distribution in mouse retinas. From their counts, Carter-Dawson and LaVail [5] inferred that cone density must drop gradually from the central to the peripheral portions of the mouse retina. A more detailed examination of the spatial patterning of mouse cones verified this conclusion [7]. Cell counts made at 15 locations along a vertical meridian bisecting the center of the retina revealed a centroperipheral decline in cone density that encompasses less than a factor of two, with densities falling from about 15,000/mm2 in the central retina to about 8,000/mm2 at the far periphery. Other investigators have reported higher peak cone densities in the mouse retina (range of 22,000– 24,000/mm2) with a slightly steeper falloff in cone density toward the peripheral retina [9]. For comparative context, cone densities achieve peak values of about 200,000/mm2 in the human retina, dropping then to less than 5,000/mm2 in the periphery [10]. There is also a centroperipheral decline in the density of mouse rods paralleling that of the cones. Overall, mouse rods have an average density of about 437,000 cells/mm2, reaching peak densities that are more than twice that of the rods in the human retina. The retinal image magnification factor for C57/BL6 mice has been calculated to have a value of 34 m/deg [11], and consequently, information gleaned from mouse photoreceptor density maps can be used to calculate the actual numbers of photoreceptors stimulated for various patterns of retinal illumination.
Mouse Strain Variations
The mouse strain C57/BL6 is acknowledged to be the most widely used of all inbred strains and that also seems likely to be the case for retinal research. Accordingly, unless otherwise specifically indicated, that strain can be assumed to have been the target animal in this chapter. It is worth noting that, setting aside those mouse strains that carry specific mutations affecting cone numbers, there are likely other strain differences that have an impact on cone-based vision. Suggestive evidence for that inference comes from a comparative study of 50 mouse strains that revealed there are strain differences in eye size [12], and one consequence of that is a striking between-strain variation in retinal area (ranging from 15.5 to 21.5 mm2). Although cone populations were not specifically assessed in this work, the clear implication is that there are considerable strain variations in overall cone numbers. Whether there are also strain differences in cone density and cone distribution seems so far unknown. Given there are known strain-related differences in overall ganglion cell numbers [13], similar variations in cone populations would not be surprising. An additional important fact is that mouse eyes continue to grow (albeit with a continuously decreasing rate) for a very significant portion of the life span [13]. Such change holds potential implications for functional studies of mouse vision in which age is either a controlled or uncontrolled variable.