Peter Kozulin

The University of Queensland, Australia, Queensland Brain Institute, Post-Doc

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My recent research has focused on the development and evolution of commissural neurons within the mammalian nervous system. In particular, I am interested in the regulatory mechanisms that control the specification and arealisation of these neurons, and the molecular signalling that underlies these processes. I am also interested in understanding how changes in transcription regulatory processes have contributed to the evolution of commissural tracts in mammals.

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Henk Bolhuis

Royal Netherlands Academy of Arts and Sciences

Maria Brincker

University of Massachusetts, Boston

Lynne Schepartz

University of the Witwatersrand

Jeffrey Townsend

Yale University

Christina Richards

University of South Florida

Cemal ÜN

Ege University

Nuray Sogunmez

Kadir Has University

Pınar Öz

Üsküdar University, İstanbul, TURKEY

Carlos Araya

Stanford University

Lana Ruck

Indiana University

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Papers by Peter Kozulin

Axonal Guidance: Making Connections

Neuroscience in the 21st Century, 2016

Investigating Early Formation of the Cerebral Cortex by In Utero Electroporation: Methods and Protocols

Neuromethods, 2016

Gene Expression in Central vs Peripheral Primate Retina - Defining the Foveal Avascular Zone

by Peter Kozulin and Jan Provis

Journal of Vision, 2010

Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens

Molecular vision, 2010

To examine in detail the time-course of changes in Zif268, Egr-1, NGFI-A, and Krox-24 (ZENK) and ... more To examine in detail the time-course of changes in Zif268, Egr-1, NGFI-A, and Krox-24 (ZENK) and pre-proglucagon (PPG) RNA transcript levels in the chick retina during periods of increased ocular growth induced by form-deprivation and negative-lens wear. To further elucidate the role of ZENK in the modulation of ocular growth, we investigated the effect of intravitreal injections of the muscarinic antagonist atropine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN), both of which block the development of experimental myopia, on the expression of ZENK in eyes fitted with negative-lenses. Myopia was induced by fitting translucent diffusers or -10D polymethyl methacrylate (PMMA) lenses over one eye of the chicken. At times from 1 h to 10 days after fitting of the diffusers or negative lenses, retinal RNA transcript levels of the selected genes were determined by semi-quantitative real-time reverse transcriptase polymerase chain reaction (...

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Gradients of Eph-A6 expression in primate retina suggest roles in both vascular and axon guidance

by Peter Kozulin and Michele Madigan

Molecular vision, 2009

Recently we identified high levels of expression of Eph-A6 in the macula of developing human reti... more Recently we identified high levels of expression of Eph-A6 in the macula of developing human retina and showed localization of Eph-A6 to ganglion cells (GC). In the present study we investigated the expression of some members of the ephrin family in developing primate retina, including the topography of Eph-A6 expression, and its ligands, in developing macaque retinas. We extracted RNA from human fetal retinas and probed for Eph-A5-A7, Eph-B1, ephrin-B2, and ephrin-A1-A5 by RT-PCR, then prepared riboprobes for Eph-A5-A7, Eph-B1 and ephrin-A1, -A4 and -B2. Paraffin sections of fetal macaque retinas were used to localize expression of Ephs and ephrins by in situ hybridization and immunohistochemistry. We identified prominent gradients of Eph-A6 mRNA expression in the ganglion cell layer (GCL) of fetal macaque retinas of different ages. The gradient of Eph-A6 expression was high near the optic disc and low at the developing macula at fetal day (Fd) 55. At Fd 70 and 80, the gradient of ...

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Differential expression of anti-angiogenic factors and guidance genes in the developing macula

by Peter Kozulin and Michele Madigan

Molecular vision, 2009

The primate retina contains a specialized, cone-rich macula, which mediates high acuity and color... more The primate retina contains a specialized, cone-rich macula, which mediates high acuity and color vision. The spatial resolution provided by the neural retina at the macula is optimized by stereotyped retinal blood vessel and ganglion cell axon patterning, which radiate away from the macula and reduce shadowing of macular photoreceptors. However, the genes that mediate these specializations, and the reasons for the vulnerability of the macula to degenerative disease, remain obscure. The aim of this study was to identify novel genes that may influence retinal vascular patterning and definition of the foveal avascular area. We used RNA from human fetal retinas at 19-20 weeks of gestation (WG; n=4) to measure differential gene expression in the macula, a region nasal to disc (nasal) and in the surrounding retina (surround) by hybridization to 12 GeneChip microarrays (HG-U133 Plus 2.0). The raw data was subjected to quality control assessment and preprocessing, using GC-RMA. We then use...

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Differential gene expression in the developing human macula: microarray analysis using rare tissue samples

The macula is a unique and important region in the primate retina that achieves high resolution a... more The macula is a unique and important region in the primate retina that achieves high resolution and color vision in the central visual field. We recently reported data obtained from microarray analysis of gene expression in the macula of the human fetal retina (Kozulin et al., Mol Vis 15:45-59, 1). In this paper, we describe the preliminary analyses undertaken to visualize differences and verify comparability of the replicates used in that study, report the differential expression of other gene families obtained from the analysis, and show the reproducibility of our findings in several gene families by quantitative real-time PCR.

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Effects of a Head-Mounted Display on the Oculomotor System of Children

Optometry and Vision Science, 2009

This study evaluated the effects of short term and extended viewing of virtual imagery using the ... more This study evaluated the effects of short term and extended viewing of virtual imagery using the Binocular Viewer (new generation bi-ocular viewer) on the visual system of children, and compared these effects with that of viewing a high definition television (HDTV) display. Sixty children aged 5 to 16 years viewed 30 min of virtual imagery using the Binocular Viewer and a HDTV display on two occasions. Sixteen subjects, aged 13 to 16 years, completed a third session of extended viewing (80 min) with the Binocular Viewer. Oculomotor function and symptoms were assessed previewing, immediately postviewing, and 10 min postviewing. Thirty minutes of Binocular Viewer use resulted in symptom increases (p &amp;amp;amp;amp;amp;amp;lt; 0.05) immediately postviewing (&amp;amp;amp;amp;amp;amp;quot;feeling tired,&amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;quot;feeling sleepy,&amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;quot;difficulty concentrating,&amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;quot;sore/aching eyes&amp;amp;amp;amp;amp;amp;quot;) however most symptoms had dissipated by 10-min postviewing. There were no significant symptom differences between viewing with the Binocular Viewer and the HDTV display at either time point. An increase in symptoms (p &amp;amp;amp;amp;amp;amp;lt; 0.05) immediately postviewing was recorded after 80 min of Binocular Viewer use (&amp;amp;amp;amp;amp;amp;quot;feeling tired,&amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;quot;feeling bored,&amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;quot;feeling sleepy,&amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;quot;tired eyes&amp;amp;amp;amp;amp;amp;quot;), however only &amp;amp;amp;amp;amp;amp;quot;feeling tired&amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;quot;feeling bored&amp;amp;amp;amp;amp;amp;quot; remained significantly increased (p &amp;amp;amp;amp;amp;amp;lt; 0.05) 10-min postviewing. Near unaided visual acuity demonstrated a significant and consistent reduction immediately (p &amp;amp;amp;amp;amp;amp;lt; 0.01) and at 10 min (p &amp;amp;amp;amp;amp;amp;lt; 0.05) following 30 min of Binocular Viewer use and immediately following 80 min of use (p &amp;amp;amp;amp;amp;amp;lt; 0.01). Near unaided VA was also significantly reduced (p &amp;amp;amp;amp;amp;amp;lt; 0.01) immediately after 30 min of HDTV display use. Virtual imagery viewing with the Binocular Viewer in children aged 5 to 16 years had few additional adverse effects when compared to viewing a more conventional HDTV display. The Binocular Viewer was comfortable to wear for up to 80 min of viewing. The consistent reduction in near vision for both viewing durations with the Binocular Viewer requires further investigation.

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The Cellular Expression of Antiangiogenic Factors in Fetal Primate Macula

Investigative Ophthalmology & Visual Science, 2010

To characterize the cellular expression patterns of antiangiogenic factors differentially regulat... more To characterize the cellular expression patterns of antiangiogenic factors differentially regulated in the fetal human macula. METHODS. RNA was extracted from macular, nasal, and surround biopsies of three human fetal retinas at midgestation. Relative levels of expression of pigment epithelium-derived factor (PEDF), brain natriuretic peptide (BNP), collagen type IV␣2 (COL4A2), and natriuretic peptide receptors A and C (NPRA and NPRC) were determined with quantitative PCR. Cellular expression of PEDF and BNP was investigated by in situ hybridization on retinal sections from monkeys aged between fetal day 55 and 11 years. BNP, COL4A2, and NPRA proteins were localized by immunohistochemistry. Labeling was imaged and quantified by confocal microscopy and optical densitometry. RESULTS. Quantitative PCR confirmed higher levels of PEDF and BNP and lower levels of COL4A2 in the macula at midgestation. PEDF mRNA was detected in ganglion cells (GCs) and the pigment epithelium (RPE). BNP mRNA was detected in GCs and macroglia, although BNP immunoreactivity (IR) was predominantly perivascular. COL4A2-IR was detected in large blood vessels and NPRA-IR on the retinal vascular endothelium, GC axons in fetal retinas, and cone axons at all ages. Optical densitometry showed a graded expression of PEDF and BNP at all ages, with highest levels of expression in GCs in the developing fovea. CONCLUSIONS. Because the retinal vessels initially form in the GC layer, it is likely that PEDF has a key role in defining and maintaining the foveal avascular area. The precise role of BNP is unclear, but it may include both antiangiogenic and natriuretic functions. (Invest Ophthalmol Vis Sci. the 21 WG retina was fixed in 2% paraformaldehyde and prepared as a wholemount.

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Analysis of Complement Expression in Light-Induced Retinal Degeneration: Synthesis and Deposition of C3 by Microglia/Macrophages Is Associated with Focal Photoreceptor Degeneration

by Krisztina Valter, Peter Kozulin, Matt Rutar, and Paul Gatenby

Investigative Ophthalmology & Visual Science, 2011

To investigate the expression and localization of complement system mRNA and protein in a light-i... more To investigate the expression and localization of complement system mRNA and protein in a light-induced model of progressive retinal degeneration. METHODS. Sprague-Dawley (SD) rats were exposed to 1000 lux of bright continuous light (BCL) for up to 24 hours. At time points during (1-24 hours) and after (3 and 7 days) exposure, the animals were euthanatized and the retinas processed. Differential expression of complement genes at 24 hours of exposure was assessed using microarray analysis. Expression of complement genes was validated by quantitative PCR, and expression of selected genes was investigated during and after BCL exposure. Photoreceptor apoptosis was assessed using TUNEL and C3 was further investigated by spatiotemporal analysis using in situ hybridization and immunohistochemistry. RESULTS. Exposure to 24 hours of BCL induced differential expression of a suite of complement system genes, including classic and lectin components, regulators, and receptors. C1qr1, MCP, Daf1, and C1qTNF6 all modulated in concert with photoreceptor death and AP-1 expression, which reached a peak at 24 hours exposure. C1s and C4a reached peak expression at 3 days after exposure, while expression of C3, C3ar1, and C5r1 were maximum at 7 days after exposure. C3 mRNA was detected in ED1-and IBA1-positive microglia/macrophages, in the retinal vessels and optic nerve head and in the subretinal space, particularly at the margins of the emerging lesion. CONCLUSIONS. The data indicate that BCL induces the prolonged expression of a range of complement genes and show that microglia/macrophages synthesize C3 and deposit it in the ONL after BCL injury. These findings have relevance to the role of complement in progressive retinal degeneration, including atrophic AMD. (Invest Ophthalmol Vis Sci.

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Axonal Guidance: Making Connections

Neuroscience in the 21st Century, 2016

Investigating Early Formation of the Cerebral Cortex by In Utero Electroporation: Methods and Protocols

Neuromethods, 2016

Gene Expression in Central vs Peripheral Primate Retina - Defining the Foveal Avascular Zone

by Peter Kozulin and Jan Provis

Journal of Vision, 2010

Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens

Molecular vision, 2010

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Gradients of Eph-A6 expression in primate retina suggest roles in both vascular and axon guidance