Effects of optical defocus on refractive development in monkeys: evidence for local, regionally selective mechanisms.

PURPOSE: To characterize the influence of optical defocus on ocular shape and the pattern of peripheral refraction in infant rhesus monkeys. METHODS: Starting at 3 weeks of age, eight infant monkeys were reared wearing -3 diopter (D) spectacle lenses over one eye that produced relative hyperopic defocus in the nasal field (NF) but allowed unrestricted vision in the temporal field (NF group). Six infants were reared with monocular -3 D lenses that produced relative hyperopic defocus across the entire field of view. Control data were obtained from 11 normal monkeys. Refractive development was assessed by streak retinoscopy performed along the pupillary axis and at eccentricities of 15 degrees, 30 degrees, and 45 degrees along the vertical and horizontal meridians. Central axial dimensions and eye shape were assessed with magnetic resonance imaging. RESULTS: In response to full-field hyperopic defocus, the eye developed relative central axial myopia, became less oblate, and exhibited relative peripheral hyperopia in both the nasal and the temporal hemifields. Conversely, nasal-field hyperopic defocus produced relative myopia that was largely restricted to the nasal hemifield; these alterations in the patterns of peripheral refraction in the NF monkeys were associated with local, region-specific alterations in vitreous chamber depth in the treated hemiretina. CONCLUSIONS: Optically imposed defocus can alter the shape and pattern of peripheral refraction in infant primates. Like those of form deprivation, the effects of optical defocus in primates are dominated by mechanisms that integrate visual signals in a spatially restricted manner and exert their influence in a regionally selective manner.

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis.

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis ("flesh-eating disease"). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the DeltamtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.

Hemiretinal form deprivation: evidence for local control of eye growth and refractive development in infant monkeys.

PURPOSE: To determine whether refractive development in primates is mediated by local retinal mechanisms, the authors examined the effects of hemiretinal form deprivation on ocular growth and the pattern of peripheral refractions in rhesus monkeys. METHODS: Beginning at approximately 3 weeks of age, nine infant monkeys were reared wearing monocular diffuser lenses that eliminated form vision in the nasal field (nasal field diffuser [NFD]). Control data were obtained from the nontreated fellow eyes, 24 normal monkeys, and 19 monkeys treated with full-field diffusers. Refractive development was assessed by retinoscopy performed along the pupillary axis and at eccentricities of 15 degrees, 30 degrees, and 45 degrees. Central axial dimensions and eye shape were assessed by A-scan ultrasonography and magnetic resonance imaging, respectively. RESULTS: Hemiretinal form deprivation altered refractive development in a regionally selective manner, typically producing myopia in the treated hemifields. In particular, six of the NFD monkeys exhibited substantial amounts (-1.81 to -9.00 D) of relative myopia in the nasal field that were most obvious at the 15 degrees and 30 degrees nasal field eccentricities. The other three NFD monkeys exhibited small amounts of relative hyperopia in the treated field. The alterations in peripheral refraction were associated with local, region-specific alterations in vitreous chamber depth in the treated hemiretina. CONCLUSIONS: The effects of form deprivation on refractive development and eye growth in primates are mediated by mechanisms, presumably retinal, that integrate visual signals in a spatially restricted manner and exert their influence locally.

Effects of form deprivation on peripheral refractions and ocular shape in infant rhesus monkeys (Macaca mulatta).

PURPOSE: To determine whether visual experience can alter ocular shape and peripheral refractive error pattern, the authors investigated the effects of form deprivation on refractive development in infant rhesus monkeys. METHODS: Monocular form deprivation was imposed in 10 rhesus monkeys by securing diffuser lenses in front of their treated eyes between 22 +/- 2 and 163 +/- 17 days of age. Each eye's refractive status was measured longitudinally by retinoscopy along the pupillary axis and at 15 degrees intervals along the horizontal meridian to eccentricities of 45 degrees . Control data for peripheral refraction were obtained from the nontreated fellow eyes and six untreated monkeys. Near the end of the diffuser-rearing period, the shape of the posterior globe was assessed by magnetic resonance imaging. Central axial dimensions were also determined by A-scan ultrasonography. RESULTS: Form deprivation produced interocular differences in central refractive errors that varied between +2.69 and -10.31 D (treated eye-fellow eye). All seven diffuser-reared monkeys that developed at least 2.00 D of relative central axial myopia also showed relative hyperopia in the periphery that increased in magnitude with eccentricity. Alterations in peripheral refraction were highly correlated with eccentricity-dependent changes in vitreous chamber depth and the shape of the posterior globe. CONCLUSIONS: Like humans with myopia, monkeys with form-deprivation myopia exhibit relative peripheral hyperopia and eyes that are less oblate and more prolate. Thus, in addition to producing central refractive errors, abnormal visual experience can alter the shape of the posterior globe and the pattern of peripheral refractive errors in infant primates.