The semidominant mutation Krd (kidney and retinal defects) was identified in transgenic line Tg8052. Krd/+ mice have a high incidence of kidney defects including aplastic, hypoplastic, and cystic kidneys. Retinal defects in Krd/+ mice include abnormal electroretinograms and a reduction of cell numbers that is most extreme in the inner cell and ganglion layers. Viability of Krd/+ mice is strongly influenced by genetic background, and growth retardation is observed in young animals. Homozygosity results in early embryonic lethality. Fluorescence in situ hybridization of a transgene-specific probe localized the insertion site to the distal region of mouse Chromosome 19. The sequence of the insertion site revealed transgene insertion into a LINE element with deletion of a single nucleotide from the 3' terminus of the transgene. A polymorphic microsatellite, D19Umi1, was identified in a junction clone and mapped in several large crosses. D19Umi1 is located 1.7 +/- 1.0 cM distal to Pax2, which encodes a paired type transcription factor expressed in embryonic kidney and eye. Deletion of Pax2 from the transgenic chromosome was demonstrated by Southern analysis of genomic DNA from (Krd/+ x SPRET/Ei)F1 mice. Additional genetic and molecular data are consistent with an approximately 7-cM deletion that includes the loci stearoyl CoA desaturase (Scd1), pale ear (ep), D19Mit17, D19Mit24, D19Mit27, D19Mit11, and Pax2. This deletion, Del(19)TgN8052Mm, will be useful for genetic and functional studies of this region of mouse Chromosome 19.

We develop formulas for calculating the approximate depth of focus of any eye. They show that the magnitude of depth of focus is inversely proportional to the size of the eye and to its visual acuity. One particular implication of these quantitative relations. which is supported by previous data from rats and human infants, is that small eyes with low acuity should have large depths of focus. We show that the observed relation between defocus and contrast sensitivity in rats in predicted by our formulas. We also analyze recent findings in human infants and show that they demonstrate a good correspondence between the improvement in accuracy of the accommodative responx with age and the reduction in depth of focus (predicted from our formulas) as acuity and eye size increase over the same age range. Optical factors such as astigmatism, refractive error and chromatic and spherical aberration should have no effect on visual resolution unless they exceed the depth of focus of an eye. Thus, our arguments imply that these factors may be relatively unimportant in small eyes with low acuity.

A dominant form of human congenital nightblindness is caused by a gly903asp (G90D) mutation in rhodopsin. G90D has been shown to activate the phototransduction cascade in the absence of light in vitro. Such constitutive activity of G90D rhodopsin in vivo would desensitize rod photoreceptors and lead to nightblindness. In contrast, other rhodopsin mutations typically give rise to nightblindness by causing rod cell death. Thus, the proposed desensitization without rod degeneration would be a novel mechanism for this disorder. To explore this possibility, we induced mice to express G90D opsin in their rods and then examined rod function and morphology, after first crossing the transgenic animals with rhodopsin knock-out mice to obtain appropriate levels of opsin expression. The G90D mouse opsin bound the chromophore and formed a bleachable visual pigment with max of 492 nm that supported rod photoresponses. (Gϩ/Ϫ, Rϩ/Ϫ) retinas, heterozygous for both G90D and wildtype (WT) rhodopsin, possessed normal numbers of photoreceptors and had a normal rhodopsin complement but exhibited considerable loss of rod sensitivity as measured electroretinographically. The rod photoresponses were desensitized, and the response time to peak was faster than in (Rϩ/Ϫ) animals. An equivalent desensitization resulted by exposing WT retinas to a background light producing 82 photoisomerizations rod Ϫ1 sec Ϫ1 , suggesting that G90D rods in darkness act as if they are partially "light-adapted." Adding a second G90D allele gave (Gϩ/ϩ, Rϩ/Ϫ) animals that exhibited a further increase of equivalent background light level but had no rod cell loss by 24 weeks of age. (Gϩ/ϩ, RϪ/Ϫ) retinas that express only the mutant rhodopsin develop normal rod outer segments and show minimal rod cell loss even at 1 year of age. We conclude that G90D is constitutively active in mouse rods in vivo but that it does not cause significant rod degeneration. Instead, G90D desensitizes rods by a process equivalent to light adaptation.

SUMMARY1. The visual acuity of the peripheral retina was measured using both sinusoidal gratings viewed in the usual way and interference fringes formed on the retina directly.2. It is shown that optical aberrations cause a reduction in peripheral visual acuity for eccentricities of less than 5°. However, the hypothesis that optical defects are a major cause of the well-known decrease in acuity with eccentricity is rejected.3. The fringe acuities at various retinal positions are compared with Osterberg's counts of the distribution of cones. It is shown that at eccentricities of less than 20, resolution approaches the theoretical limits for a mosaic of receptors. INTRODIUCTIONThe resolving power of the human eye is greatest in the fovea and falls off rapidly with increasing angular distance from the point of fixation. This fall in visual acuity with eccentricity is usually explained as being due to both the fall in density of cones and the changes in synaptic organization as one moves away from the fovea. However, in addition there is a third possible factor to be considered. The quality of the images formed on the retina might vary with eccentricity. Even on the fovea optical factors are important determinants of visual resolving capacity (Campbell & Green, 1965). In addition to the aberration of the foveal image, peripheral imagery involves off-axis aberrations, such as oblique astigmatism and coma, of unknown magnitudes.To determine how optical factors limit the intrinsic abilities ofthe human eye to appreciate fine detail the visual acuity of the peripheral retina has been measured in two ways. First, a gas laser was used to produce sinusoidal interference fringes directly on the retina. The fringes on the retina PHY 207 I2