Bay Area Vision Research Day: Wednesday, August 10th, 2011
Photo Courtesy University of California, Berkeley
BAVRD is an annual one-day meeting hosted by the Vision Science graduate program at UC Berkeley, dedicated to fostering community amongst researchers in the San Francisco Bay Area in vision-related fields including neuroscience, ophthalmology, psychology, optics, and computer vision.
Schedule: (Wednesday August 10th, 2011)
9:10a:Matilda Chan, M.D., Ph.D., UC San Francisco "Role of Macrophage Elastase (MMP12) in Corneal Myeloid Cell Activities Visualized With Time-lapse in vivo Confocal Microscopy"
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"Purpose: To analyze myeloid cell activity in response to corneal chemical injury and to investigate the role of macrophage elastase (MMP12).
Methods: Corneal expression of MMP12 in wild-type (WT) mice following chemical injury was assayed using quantitative real-time PCR (qPCR). Corneal macrophage infiltration of injured WT and MMP12-/- mice was quantified using whole-mount immunofluorescence staining (F4/80 antibody) and flow cytometry. Relative expression levels of CC chemokines were compared using qPCR and protein arrays. Mice expressing EGFP under the c-fms promoter were crossed with the MMP12 line to generate WT and MMP12-/- mice expressing EGFP-labeled myeloid cells to visualize these cells in the corneal stroma. Myeloid cell activity was documented in vivo with time-lapse confocal microscopy (20-90 minute duration) before and 1 day after injury. Imaging software (Imaris) was used to create movies tracking cell movement.
Results: MMP12 expression levels following corneal chemical injury of WT mice showed peak expression levels occurring 2 and 6 days after injury. Injured corneas of MMP12-/- mice demonstrated increased macrophage infiltration compared with WT mice. Members of the CC chemokine family were screened and higher levels of monocyte chemoattractant protein-1 (MCP-1 or CCL2) were detected in wounded corneas of MMP12-/- mice. In vivo time-lapse confocal microscopy allowed visualization and comparison of myeloid cell behavior in WT and MMP12-/- mice. Resident corneal myeloid cells of non-injured WT and MMP12-/- mice displayed minimal movement. One day after chemical injury, myeloid cells of WT mice were active and had increased track length. In contrast, myeloid cells of injured MMP12-/- mouse corneas remained minimally active and tracking plots showed little migration.
Conclusions: MMP12 deficient mice had elevated CCL2 expression and increased corneal macrophage accumulation in response to chemical injury suggesting a role for MMP12 in the regulation and distribution of myeloid cells. We were able to monitor in vivo myeloid cell activities using time-lapse confocal microscopy. Upon injury, myeloid cells in WT mice became more migratory likely representing a scavenger response. Myeloid cells of MMP12-/- mice, however, remained minimally migratory which may reflect a difference in macrophage M1 and M2 polarization. These findings suggest an important role for MMP12 in the regulation of myeloid cell activities in the corneal healing response."
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"Purpose: To analyze myeloid cell activity in response to corneal chemical injury and to investigate the role of macrophage elastase (MMP12).
Methods: Corneal expression of MMP12 in wild-type (WT) mice following chemical injury was assayed using quantitative real-time PCR (qPCR). Corneal macrophage infiltration of injured WT and MMP12-/- mice was quantified using whole-mount immunofluorescence staining (F4/80 antibody) and flow cytometry. Relative expression levels of CC chemokines were compared using qPCR and protein arrays. Mice expressing EGFP under the c-fms promoter were crossed with the MMP12 line to generate WT and MMP12-/- mice expressing EGFP-labeled myeloid cells to visualize these cells in the corneal stroma. Myeloid cell activity was documented in vivo with time-lapse confocal microscopy (20-90 minute duration) before and 1 day after injury. Imaging software (Imaris) was used to create movies tracking cell movement.
9:30a:Suzanne Fleiszig, O.D., Ph.D., UC Berkeley "Bacteria versus the ocular surface: Who wins and why?"
8:30 am - 9:00 am: Check-in and Breakfast (at Stanley Hall)
9:00 am - 9:10 am: Welcome and Introduction
9:10 am - 10:10 am: Talk Session I: Anterior Segment
9:50a:Clayton Radke, Ph.D., UC Berkeley "Are Your Patient's Tears Too Salty?
- Starting with the pioneering efforts of Gilbard in 1978, hyperosmotic tear has been implicated in the etiology of dry-eye syndrome. Continuing effort has strengthened this implication so that tear hyperosmolarity is now included in the definition of dry eye (DEWS, 2007) both for evaporative dye eye (EDE) and for aqueous deficient dry eye (ADDE). Current literature on tear hyperosmolarity expands almost daily. We present physical reasoning explaining how tear osmolarity is set in homeostasis and what factors control tear hyperosmolarity including relative humidity, blink rate, tear supply, lipid health, contact-lens wear, etc. Discussion is addressed to whether tear osmolarity should be used clinically as a diagnosis of dry eye.
10:10 am - 10:30 am: Coffee Break
10:30 am - 11:30 pm: Talk Session II: Retina I
10:30a:Robert Zawadzki, Ph.D., UC Davis "Progress on high resolution in-vivo retinal imaging at UC Davis VRSI"
- Recent advances in resolution; acquisition speed as well as detection techniques used for imaging of the living human eye have begun transforming the diagnosis and treatment of retinal diseases. In this talk we will briefly present recent progress on developing high-resolution in- vivo retinal imaging systems. This includes a novel contrast agent-free method, phase-contrast OCT (pv-OCT), that allows visualization of retinal blood perfusion up to the smallest capillaries as well as recent improvements we made to the UC Davis multimodal adaptive optics imaging system (combining OCT and SLO), that allows imaging of cellular resolution structures in 3D in the living human eye. Examples of applying these instruments for retinal imaging will be presented. Possible directions for future system development will be discussed as well.
10:50a:Jacque Duncan, M.D., UC San Francisco "Cone Structure in Patients with BEST1 Mutations"
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Purpose: To study macular structure and function in patients with mutations in the BEST1 gene.
Methods: the coding sequences of the BEST1 gene were bidirectionally sequencedin 6 patients from 4 families with bilateral vitelliform maculopathy. Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SDOCT) images were compared with normal subjects. Fundus autofluorescence (AF), visual acuity (VA), kinetic and static perimetry, electro-oculography (EOG), full-field (ffERG) and multifocal electroretinography (mfERG) were measured.
Results: Heterozygous mutations in BEST1 were present in all patients (Patient 1, Glu292Lys; Patient 2, Arg218His; Patients 3 and 4, Glu300Lys; Patients 5 and 6, Val9Ala). VA ranged from 20/20-20/125. Vitelliform subretinal deposits were present in all patients; retinal pigment epithelium (RPE) atrophy was present in at least 1 eye of all but the youngest patient. Arden ratios were reduced, ffERG amplitudes and timing were normal and mfERG amplitudes were reduced with delayed timing in the affected areas. AF was increased centrally in all patients; some showed reduced AF within the hyperAF lesion consistent with RPE atrophy. 4 of 6 patients maintained foveal fixation while fixation was eccentric in 2 patients. VA was best in those without subretinal fluid, but was 20/25 in the presence of subretinal fluid where hyperreflective outer segments were observed adjacent to the fovea. Patients with reduced VA showed subretinal or subRPE fluid and loss of the outer segment layer. Cones in vitelliform lesions were generally weakly reflective and of low density, except in the youngest patient who had discrete, highly reflective, contiguous patches of cones, some with normal spacing. Cones outside lesions were generally contiguous and close packed, but cone density was decreased where there was either increased AF or subretinal fluid. Cones were most normal at the borders of macular lesions without subretinal fluid and where AF was most normal.
Conclusions: AOSLO showed well-preserved cones outside regions with AF deposits, subretinal fluid or photoreceptor/RPE atrophy in patients with BEST1 mutations, suggesting AF abnormalities and subretinal fluid are associated with cone loss.
11:10a:Alexander Sher, Ph.D., UC Santa Cruz "Retinal Plasticity and Restoration of Function after Photocoagulation"
- "Neural plasticity in mammalian adult central nervous system underlies processes of learning, memory formation, and changes due to disease or injury. In the retina, plasticity induced by injury or disease is known to be mostly destructive, i.e. leading to abnormal retinal function and structure. However, recent studies showed that anatomical continuity of the rabbit and rodent retina might be restored after selective photocoagulation. Unlike more intense conventional burns, such photocoagulation destroys only photoreceptors and retinal pigment epithelium (RPE), leaving the inner retinal layers intact. Our data indicates that following selective photocoagulation in the rabbit retina, the migrating cone photoreceptors lead to restoration of visual sensitivity over the lesion, and make new functional synapses to bipolar cells that are located inside the lesion and have initially lost their pre-synaptic photoreceptors."
11:30 pm - 1:00 pm: Lunch and poster setup
1:00 pm - 2:20 pm: Talk Session III: Retina II
1:00p:Jan Verweij, UC San Francisco "Gap-junctional coupling of mammalian rod photoreceptors and its effect on visual detection"
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Background: Gap junctions between rods in mammalian retina suggests a role for rod-rod coupling in human vision. Rod coupling is known to reduce response variability, but because junctional conductances are not known, the downstream effects on visual performance are uncertain.
Methods: We assessed rod coupling in guinea pig retina by: 1) analysis of the variability in dim flash responses, 2) measurement of junctional conductances, and 3) Neurobiotin tracer coupling. Results were consolidated into an electrical network model and a model of human psychophysical detection.
Results and conclusion: Guinea pig rods form networks of 1-15 rods, with junctional conductances averaging ~350 pS. We calculate that coupling will reduce human dark-adapted sensitivity ~10% by impairing the noise-filtering of the synapse. However, coupling also circumvents synaptic saturation and is thus calculated to improve sensitivity when stimuli are spatially restricted or are superimposed on background illumination.
1:20p:James Long, Ph.D., UC San Francisco "Transmission at the rod-to-rod bipolar synapse in mice lacking phosducin"
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"Background:
Recent work has shown that dark-adapted ERG b-waves recorded from mice lacking the phosphoprotein phosducin (Pd-/-) have smaller amplitudes than wild-type (Wt) controls and exhibit impaired light adaptation. Because phosducin is expressed in photoreceptors but not second-order visual neurons, it was hypothesized that phosducin acts presynaptically to modulate transmission between rods and on-bipolar cells.
Methods: To test this hypothesis directly, we used whole-cell patch clamp recordings to measure light-evoked currents from both wild-type (Wt) and phosducin knockout (Pd-/-) rod bipolar cells (RBCs) in the absence and presence of background light.
Results: We found that the average dim flash response of RBCs from Pd-/- mice is 42% smaller than in Wt controls. This result can be accounted for by the implementation of a standard model of the threshold-like nonlinearity at the rod to RBC synapse together with previous work demonstrating a reduction in signal amplification in Pd-/- rod outer segments. In addition, we observed a 1.9-fold increase in the background light intensity required to suppress half of the response amplitude to a bright flash of light in Pd-/- RBCs. This corresponds closely to previous work demonstrating a 1.6-fold increase in the background light intensity required to reduce the sensitivity of Pd-/- rod outer segments to that measured in Wt controls.
Conclusions: The changes in sensitivity and light adaptation observed in Pd-/- RBCs can be accounted for by a previously observed decreases in the sensitivity of Pd-/- rod outer segments and do not support the hypothesis that phosducin modulates transmission at the rod to RBC synapse in a retinal slice preparation."
1:40p:Alan Horsager, Ph.D., USC "Virally-Delivered Channel rhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness"
- Previous work established retinal expression of Channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, developing a viable ChR2-based human therapy must meet several key criteria: 1) ChR2 expression must be targeted, robust, and long-term, 2) ChR2 must provide long-term and continuous therapeutic efficacy, and 3) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector packaged in a tyrosine-mutated capsid. Targeted expression lead to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months post injection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was non-toxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness.
2:00p:Daniel Palanker, Ph.D., Stanford "Photovoltaic Retinal Prosthesis for Restoring Sight"
- Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensation. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with pixel density as high as 256 pix/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky power supplies, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected onto retina by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (16, 64, and 256 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded spikes elicited from the ganglion cells, with latencies in the 2-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 15Hz the average irradiance is more than two orders of magnitude below the retinal safety limit. Neural responses were elicited with spot sizes as small as 60µm, demonstrating the possibility of a fully-integrated high- resolution photovoltaic retinal prosthesis. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that stimulation is mediated by retinal network, and raising hopes that the prosthesis will preserve some of the retina’s natural signal processing.
2:20 pm - 2:40 pm: Break
2:40 pm - 4:00 pm: Talk Session IV: The Brain and Visual Processing
2:40p:Martin Usrey, Ph.D., UC Davis "Attentional modulation of geniculocortical communication"
3:00p:Tirin Moore, Ph.D., Stanford "Control of visual cortical signals by prefrontal dopamine"
- A principal function of the prefrontal cortex (PFC) is executive control, and this control includes the modulation of sensory signals during goal-directed behavior. Dopamine (DA)-mediated activity within the PFC is thought to play an important role in executive control, yet whether it contributes to sensory filtering is not known. I will discuss experiments that demonstrate an involvement of dopamine- mediated PFC activity in the modulation of visual representations. Local blockade of D1 receptors within the frontal eye field (FEF) increases behavioral target selection within the corresponding part of visual space and enhances the magnitude, stimulus discriminablity and response reliability of visual responses in area V4. In contrast, local inactivation of FEF activity produces opposite effects. These results demonstrate that prefrontal D1 receptors are involved in top- down modulation of visual cortical representations.
3:20p:Jeremy Wolfe, Ph.D., Harvard "The grass is always greener on the other side of the monitor: Foraging and visual search"
- "Suppose you are picking raspberries. When is it time to move from this bush to the next one? Typically, you don’t pick every last berry on the bush. The Marginal Value Theory (MVT) from the animal foraging literature says that you leave for a new bush when the rate of success in this bush falls below the rate in the environment as a whole. We had Os picking berries on the computer screen. “Good” and “bad” berries had distinct but overlapping visual attributes (big red=good, little blue=bad, d’=2.5). Picking could be easy or hard. Travel time to the next patch could be short or long. Os’ behavior corresponded to the predictions of MVT. Then we changed the task. Now, all berries looked the same. The proportion of good berries varied from 20% to 80% in a patch but Os only discovered the nature of a berry when they picked it. Behavior in this situation violates MVT predictions. Here it seems that Os left a patch once they had picked a fixed number of “bad” berries."
3:40p:Golijeh Golarai, Ph.D., Stanford "Evidence for modulation of the distributed pattern of responses to faces in the fusiform gyrus by age of face stimuli in children"
- Functional regions in the human fusiform gyrus preferentially respond to faces. Recent studies suggest that a face selective region in the fusiform gyrus (fusiform face area, FFA) undergoes a prolonged development involving substantial increases in its spatial extent after age 7 years. However, it is unknown if this development is sensitive to the age of the face stimuli. Here we used functional magnetic resonance imaging (fMRI) to examine the development of face-, object- and place-selective responses and their distributed patterns in the fusiform gyrus of children (7 – 11 year olds, n = 10), adolescents (12 – 16 year olds, n = 11) and adults (18 – 40 year olds, n = 11). Subjects underwent fMRI in a 3T scanner as they viewed and fixated on images of faces of boys and men, objects, scenes and scrambled images presented in pseudo-randomly ordered blocks and performed a 1-back task. We drew the anatomical boundaries of the fusiform gyrus (FUS) and also functionally defined the FFA (man & boy faces > objects, p < 10-3) individually on each subject’s cortical gray matter. We found that regardless of the age of the face stimulus the volume of the right FFA was positively correlated with age and substantially larger in adults than in children and teens. This development was associated with higher response amplitudes and selectivity for faces compared to objects and also increased differentiation of the distributed patterns of response to faces versus non-face stimuli in the FUS. Importantly, an independent classifier of distributed fusiform responses showed significantly higher classification accuracy in in adults for adult faces than for child faces. Meanwhile classification accuracy for adult faces was higher in adults than in children, but similar for the two age-groups for child faces. Together, these results suggest an interaction between age of subject and of face stimuli in the distributed responses to faces in the fusiform gyrus, consistent with a prolonged development of face-selectivity during childhood and adolescence that may depend on the exposure and social relevance of various types of faces.
4:00 pm - 5:00 pm: Reception and poster session
- Chris Blair and Gideon Paul Caplovitz : The Effect of Attention on Context Dependent Synesthetic Experiences- C Cerretani, CJ Radke : Periodic Tear Dynamics Model for Healthy and Dry Eyes
- Tatiana Ecoiffier, Inho Choi, Sunju Lee, Young Hong, and Lu Chen : 9-Cis Retinoic Acid Modulates Corneal Lymphangiogenesis
- Eve A. Isham, William P. Banks, Joy J. Geng : Representational Momentum Influences the Perceived Time of Action
- Paul Ivanov and Tim Blanche : Improving gaze accuracy and predicting fixation with video-based eyetrackers
- Kevin Jones & Marian Berryhill : Task difficulty modulates the effect of transcranial direct current stimulation in visual working memory tasks
- Kelly Karns, Nancy McNamara, Amy E. Herr : Development of a Microfluidic Immunoassay for Highly Alkaline Human Tear Protein Biomarkers of Sjögren’s Syndrome
- Rachael Kendrick Harms, Laura Walker Renninger : Where we look depends on how we got there
- Caitlin W. Kiley, Bartlett D. Moore IV, Chao Sun, W. Martin Usrey : Rapid plasticity of visual responses in the lateral geniculate nucleus
- Anna A. Kosovicheva, Gerrit W. Maus, Stuart Anstis, Patrick Cavanagh, Peter U. Tse, & David Whitney : The motion-induced shift in the perceived location of a grating also shifts its aftereffect
- Cs. Kotsmar, T. Nadolski, N. Taylor, S.C. Tan, C.J. Radke : Determination of Mesh Size in Soft-Contact-Lens Hydrogels
- Leonard, Robinson, Kaiser, Hahn, McClenon, Gold, & Luck : Dissecting the role of magnocellular and parvocellular input in saccade production in schizophrenia
- J. Daniel McCarthy, Diana Michelle Cordeiro & Gideon Paul Caplovitz : Local form-motion interactions influence global form perception
- James Mun, Connie Tam, David Evans, Suzanne Fleiszig : Expression of microRNAs in human corneal epithelial cells is modified by exposure to human tear fluid and Pseudomonas aeruginosa antigens
- Weston Pack, Thom Carney, Stan Klein : Transient/Exogenous Attention Enhances Spatial Sensitivity
- S. Ravikumar, K. Akeley, M. S. Banks : Optimal Focus Cues in Multi-plane Stereoscopic Displays
- Laura Renninger, Anna Ma-Wyatt : Eye-hand coordination in AMD
- Derek Ricketson, Rachel DeVay, Lenin Dominguez-Ramirez, Jodi Nunnari : Two distinct functions of the dynamin-related protein Mgm1 in mitochondrial physiology
- Risa Sawaki, Joy J. Geng, & Steven J. Luck : Active suppression of attention after the completion of perception
- Sho C. Takatori, Clayton J. Radke : A Quasi-2D Model for Respiration of the Cornea with Contact-Lens Wear
- Tan Truong : Novel characterization of lymphatic valve formation
- Samantha Wang : Corneal macrophage subtype population exhibits sex and injury specific differences
Online Registration:
Register online (opens new page)Location/Directions:
Stanley Hall, UC Berkeley.View BAVRD 2011 in a larger map
Previous Meetings:
2011 is the 23rd annual Bay Area Vision Research Day!
Initiated in 1989 as "ARVO Day," this event was created as an opportunity to bring together local scientists for a focused recapitulation of talks and posters given at the ARVO annual meetings, and to provide a forum for exciting new findings.
Since then, the day has expanded in scope to reflect the evolution of the associated vision science fields and the interests of Bay Area researchers.
Tuesday, Aug. 17th, 2010
Saturday, Sept. 12th, 2009
Saturday, Sept. 13th, 2008 (schedule only)
Thursday, Aug. 2nd, 2007 (schedule and abstracts)
Thursday, Aug. 24th, 2006
Sunday, Sept. 18th, 2005
Thursday, Aug. 19th, 2004 (scanned schedule)
scanned cover
Friday, July 18th, 2003 (scanned schedule)
Friday, Aug. 24th, 2001 (scanned schedule)
Friday, June 26, 1998
Thursday, July 10, 1997 (scanned schedule)