Optometry and Vision Sciences - Research Publications

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    Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia
    McBrien, NA ; Jobling, AI ; Truong, HT ; Cottriall, CL ; Gentle, A (MOLECULAR VISION, 2009-03-02)
    PURPOSE: Muscarinic receptors are known to regulate several important physiologic processes in the eye. Antagonists to these receptors such as atropine and pirenzepine are effective at stopping the excessive ocular growth that results in myopia. However, their site of action is unknown. This study details ocular muscarinic subtype expression within a well documented model of eye growth and investigates their expression during early stages of myopia induction. METHODS: Total RNA was isolated from tree shrew corneal, iris/ciliary body, retinal, choroidal, and scleral tissue samples and was reverse transcribed. Using tree shrew-specific primers to the five muscarinic acetylcholine receptor subtypes (CHRM1-CHRM5), products were amplified using polymerase chain reaction (PCR) and their identity confirmed using automated sequencing. The expression of the receptor proteins (M1-M5) were also explored in the retina, choroid, and sclera using immunohistochemistry. Myopia was induced in the tree shrew for one or five days using monocular deprivation of pattern vision, and the expression of the receptor subtypes was assessed in the retina, choroid, and sclera using real-time PCR. RESULTS: All five muscarinic receptor subtypes were expressed in the iris/ciliary body, retina, choroid, and sclera while gene products corresponding to CHRM1, CHRM3, CHRM4, and CHRM5 were present in the corneal samples. The gene expression data were confirmed by immunohistochemistry with the M1-M5 proteins detected in the retina, choroid, and sclera. After one or five days of myopia development, muscarinic receptor gene expression remained unaltered in the retinal, choroidal, and scleral tissue samples. CONCLUSIONS: This study provides a comprehensive profile of muscarinic receptor gene and protein expression in tree shrew ocular tissues with all receptor subtypes found in tissues implicated in the control of eye growth. Despite the efficacy of muscarinic antagonists at inhibiting myopia development, the genes of the muscarinic receptor subtypes are neither regulated early in myopia (before measurable axial elongation) nor after significant structural change.
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    Can HMG Co-A reductase inhibitors ("statins") slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)
    Guymer, RH ; Dimitrov, PN ; Varsamidis, M ; Lim, LL ; Baird, PN ; Vingrys, AJ ; Robman, L (DOVE MEDICAL PRESS LTD, 2008)
    Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression.
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    Edge Detection in Landing Budgerigars (Melopsittacus undulatus)
    Bhagavatula, P ; Claudianos, C ; Ibbotson, M ; Srinivasan, M ; Warrant, E (PUBLIC LIBRARY SCIENCE, 2009-10-07)
    BACKGROUND: While considerable scientific effort has been devoted to studying how birds navigate over long distances, relatively little is known about how targets are detected, obstacles are avoided and smooth landings are orchestrated. Here we examine how visual features in the environment, such as contrasting edges, determine where a bird will land. METHODOLOGY/PRINCIPAL FINDINGS: Landing in budgerigars (Melopsittacus undulatus) was investigated by training them to fly from a perch to a feeder, and video-filming their landings. The feeder was placed on a grey disc that produced a contrasting edge against a uniformly blue background. We found that the birds tended to land primarily at the edge of the disc and walk to the feeder, even though the feeder was in the middle of the disc. This suggests that the birds were using the visual contrast at the boundary of the disc to target their landings. When the grey level of the disc was varied systematically, whilst keeping the blue background constant, there was one intermediate grey level at which the budgerigar's preference for the disc boundary disappeared. The budgerigars then landed randomly all over the test surface. Even though this disc is (for humans) clearly distinguishable from the blue background, it offers very little contrast against the background, in the red and green regions of the spectrum. CONCLUSIONS: We conclude that budgerigars use visual edges to target and guide landings. Calculations of photoreceptor excitation reveal that edge detection in landing budgerigars is performed by a color-blind luminance channel that sums the signals from the red and green photoreceptors, or, alternatively, receives input from the red double-cones. This finding has close parallels to vision in honeybees and primates, where edge detection and motion perception are also largely color-blind.
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    Segregation of short-wavelength-sensitive (S) cone signals in the macaque dorsal lateral geniculate nucleus
    Roy, S ; Jayakumar, J ; Martin, PR ; Dreher, B ; Saalmann, YB ; Hu, D ; Vidyasagar, TR (WILEY, 2009-10)
    An important problem in the study of the mammalian visual system is whether functionally different retinal ganglion cell types are anatomically segregated further up along the central visual pathway. It was previously demonstrated that, in a New World diurnal monkey (marmoset), the neurones carrying signals from the short-wavelength-sensitive (S) cones [blue-yellow (B/Y)-opponent cells] are predominantly located in the koniocellular layers of the dorsal lateral geniculate nucleus (LGN), whereas the red-green (R/G)-opponent cells carrying signals from the medium- and long-wavelength-sensitive cones are segregated in the parvocellular layers. Here, we used extracellular single-unit recordings followed by histological reconstruction to investigate the distribution of color-selective cells in the LGN of the macaque, an Old World diurnal monkey. Cells were classified using cone-isolating stimuli to identify their cone inputs. Our results indicate that the majority of cells carrying signals from S-cones are located either in the koniocellular layers or in the 'koniocellular bridges' that fully or partially span the parvocellular layers. By contrast, the R/G-opponent cells are located in the parvocellular layers. We conclude that anatomical segregation of B/Y- and R/G-opponent afferent signals for color vision is common to the LGNs of New World and Old World diurnal monkeys.
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    Novel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM study
    McCarty, CA ; Dowrick, A ; Cameron, J ; McGrath, B ; Robman, LD ; Dimitrov, P ; Tikellis, G ; Nicolas, C ; McNeil, J ; Guymer, R (BMC, 2008)
    BACKGROUND: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD). METHODS: Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye. RESULTS: 160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.
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    Factors influencing the experience of oscillopsia in infantile nystagmus syndrome
    Cham, KM ; Anderson, AJ ; Abel, LA (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2008-08)
    PURPOSE: Perceptual instability in infantile nystagmus syndrome (INS) has been reported occasionally. This study was conducted to examine the factors that influence perceptual stability in 18 individuals with INS. METHODS: The subjects were instructed to look continuously at a fixation LED centered in an image (38 degrees x 32 degrees ) at two luminance levels (3.25 and 0.46 cd/m(2), with 21% and 96% contrast, respectively) throughout all trials. A trial consisted of the fixation LED on, followed by a peripheral LED on, and then both LEDs off. Subjects then reported what they perceived. Five trials were conducted per contrast image. Eye movements were recorded with a limbal tracker. After testing, each subject completed a questionnaire to determine whether they ever had or were presently experiencing oscillopsia. RESULTS: Sixteen of 18 subjects reported experiencing oscillopsia on the questionnaire. In the laboratory, the percentages of trials with perceptions of motion of the LED and background were as follows: neither, 45% to 60%; background only, 15% to 30%; both, approximately 15%; and LED only, approximately 10%. Over all trials, 14/18 and 13/17 subjects experienced oscillopsia for the low- and high-contrast images, respectively (i.e., four subjects never experienced oscillopsia). The background was frequently seen moving when both images were displayed, regardless of contrast and/or condition. Trials with and without oscillopsia did not differ between the foveation periods. CONCLUSIONS: Subjects with INS may experience spatially inhomogeneous oscillopsia under certain viewing conditions. The physical attributes of the stimulus, repeated trials, different conduction times, and the role of divided attention may influence a subject's perception differently.
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    Visual Perception: Saccadic Omission - Suppression or Temporal Masking?
    Ibbotson, MR ; Cloherty, SL (CELL PRESS, 2009-06-23)
    Although we don't perceive visual stimuli during saccadic eye movements, new evidence shows that our brains do process these stimuli and they can influence our subsequent visual perception.
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    Saccadic Modulation of Neural Responses: Possible Roles in Saccadic Suppression, Enhancement, and Time Compression
    Ibbotson, MR ; Crowder, NA ; Cloherty, SL ; Price, NSC ; Mustari, MJ (SOC NEUROSCIENCE, 2008-10-22)
    Humans use saccadic eye movements to make frequent gaze changes, yet the associated full-field image motion is not perceived. The theory of saccadic suppression has been proposed to account for this phenomenon, but it is not clear whether suppression originates from a retinal signal at saccade onset or from the brain before saccade onset. Perceptually, visual sensitivity is reduced before saccades and enhanced afterward. Over the same time period, the perception of time is compressed and even inverted. We explore the origins and neural basis of these effects by recording from neurons in the dorsal medial superior temporal area (MSTd) of alert macaque monkeys. Neuronal responses to flashed presentations of a textured pattern presented at random times relative to saccades exhibit a stereotypical pattern of modulation. Response amplitudes are strongly suppressed for flashes presented up to 90 ms before saccades. Immediately after the suppression, there is a period of 200-450 ms in which flashes generate enhanced response amplitudes. Our results show that (1) MSTd is not directly suppressed, rather suppression is inherited from earlier visual areas; (2) early suppression of the visual system must be of extra-retinal origin; (3) postsaccadic enhancement of neural activity occurs in MSTd; and (4) the enhanced responses have reduced latencies. As a whole, these observations reveal response properties that could account for perceptual observations relating to presaccadic suppression, postsaccadic enhancement and time compression.
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    Functional Changes in the Retina during and after Acute Intraocular Pressure Elevation in Mice
    Kong, YX ; Crowston, JG ; Vingrys, AJ ; Trounce, IA ; Bui, BV (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2009-12)
    PURPOSE: To examine retinal function using the full-field electroretinogram (ERG) during and after acute intraocular pressure (IOP) elevation in wild-type mice. METHODS: IOP was elevated by anterior chamber cannulation in wild-type C57/BL6 mice. The pressure-function relationship was determined by IOP elevation in steps from baseline to 80 mm Hg. The rate of functional recovery was assessed for 60 minutes after an IOP spike of 50 mm Hg for 30 minutes. During and immediately after IOP elevation, scotopic ERG signals were recorded in response to dim and bright flashes (-4.54, -2.23, and 0.34 log cd x s x m(-2)) and analyzed for photoreceptoral (a-wave), ON-bipolar (b-wave), oscillatory potentials (OPs), and scotopic threshold responses (positive [p]STR/negative [n] STR). A full ERG protocol was collected 2 days before and 7 days after the single 50-mm Hg IOP spike. RESULTS: The pSTR was most sensitive to IOP elevation with 50% amplitude loss (mu) at 41 mm Hg (mu, 95% confidence limits (CL): 37.7, 45.6) followed by nSTR at 45 mm Hg (95% CL: 41.0, 49.1). pSTR was significantly more sensitive than the b-wave (95% CL: 41.4, 49.1), a-wave (95% CL: 47.6, 55.3), and OPs (95% CL: 49.6, 59.2). pSTR showed slower recovery immediately after the 50 mm Hg spike compared with the b-wave (P = 0.02). One week after the 50-mm Hg spike, pSTR (-30% +/- 6%, P < 0.001) and OP (-27% +/- 2%, P < 0.001) amplitudes were reduced, whereas other components were unaffected. CONCLUSIONS: The STR in mice is more sensitive to acute IOP elevation and recovers slower than other ERG components. Reduction in pSTR and OP amplitude at 1 week suggests persistent impairment of inner retinal function can occur after a single IOP spike.