AMD Faculty Research Interests
Peter J. Bex, Ph.D.
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Research Interests
My research employs behavioral and imaging techniques to study the human visual system in normal and abnormal development, in normal ageing and in neurodegenerative diseases. Particular emphasis is placed on the use of natural stimuli and tasks to examine the underlying mechanisms of visual processing.
Approximately 12
million people suffer central vision loss caused by Age-related
Macular Degeneration (AMD - www.eyesight.org),
a figure that is set to rise as our population ages. Treatment
of macular disease with conventional ophthalmic techniques
is of limited benefit in the majority of cases, forcing
people to depend on their poor resolution peripheral vision
and severely impairing essential tasks such as mobility,
face recognition and reading. We are developing new ways
to present information, images and text that may maximise
residual vision and independence in people with AMD. In
principle it should be possible to use magnification to
compensate for the loss of resolution in the peripheral
visual field. However, even magnified images can be completely
masked by nearby features, an effect known as crowding
, and this is particularly problematic in the peripheral
visual field. Figure 2 illustrates how difficult
it can be to disambiguate features in the periphery, especially
under crowded conditions. We are studying the visual processes
that cause crowding in an effort to develop novel ways to
present information that are not vulnerable to its effects.
Figure 2 Crowding. When you fixate the red squares, details in the top image are difficult to disambiguate in this complex scene. Identical image patches are much more visible when nearby crowding details are masked, without changing the size or contrast of the patches. This shows that it is usually crowding rather than acuity that limits vision in the peripheral visual field.
Publications
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Bex, P.J. and S.C. Dakin, Spatial interference among moving targets. Vision Research, 2005. 45 (11): p. 1385-98.
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Bex, P.J., S.C. Dakin, and A.J. Simmers, The shape and size of crowding for moving targets. Vision Research, 2003. 43 (27): p. 2895-904.
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Falkenberg, H.K., G.S. Rubin, and P.J. Bex, Acuity, crowding, reading and fixation stability. Vision Research, 2007 in press
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Falkenberg, H.K. and P.J. Bex, The Impact of Central and Peripheral Visual Field Loss on Eye Movements and Mobility While Walking Invest Ophthalmol Vis Sci 2005; 46: E-Abstract 4608.
Patricia A. D'Amore, Ph.D.
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Research Interests
The D’Amore Laboratory is investigating the pathogenesis of dry AMD
with a specific focus on the role of RPE-Bruch’s membrane
interactions. They are also working to elucidate the nature of the
interactions between the RPE and the choriocapillaris in the
maintenance of the RPE-Bruch’s membrane-choriocapillaris complex, with
particular emphasis on the role of RPE-derived VEGF.
Publications
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Ishida, S, Usui, T, Yamashiro, K, Kaji, Y, Amano, S, Ogura, Y, Hida, T, Oguchi, Y, Ambati, J, Ng, Y-S, D’Amore, PA, Shima, DT, Adamis, AP. VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced neovascularization, J Exptl Med, 2003; 198:483-489.
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Hartnett, ME, Lappas, A, Darland, DC, McColm, JR, Lovejoy, S, D’Amore, PA. Retinal pigment epithelium and endothelial cell interaction causes retinal pigment epithelial barrier dysfunction via a soluble VEGF-dependent mechanism. Exp Eye Res, 2003; 77:593-599.
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Saint-Geniez, M, D’Amore, PA. Development and pathology of the hyaloid, choroidal and retinal vasculature. Int J Dev Biol, 2004; 48:1045-1058.
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Saint-Geniez M, Maldonado A, D’Amore PA. VEGF expression and potential function in the choroids during development and in the adult. Invest Ophthal Vis Sci, 2006; 7:3135-3142.
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Saint-Geniez M, Maharaj ASR, Walshe TE, Tucker BE, Sekiyama E, Kurihara T, Darland DC, Young MJ, D’Amore PA. Endogenous VEGF is required for visual function: evidence for a survival role on Muller cells and photoreceptors. PLoS ONE, 2008, 3:1-13, PMID: 18978936.
Dong Feng Chen, M.D., Ph.D.
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Research Interests
My lab proposes to develop a novel stem cell approach for treating photoreceptor degeneration and restoring vision after macular degeneration.
Publications
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Kinouchi R, Takeda M, Yang L, Wilhelmsson U, A. Lundkvist, Pekny M, and Chen DF. (2003) Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nature Neurosci. 6, 863-868.
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Nakazawa T, Takeda M, Lewis GP, Cho K-S, Jiao J, Wilhelmsson U, Fisher SK, Pekny M, Chen DF*, and Miller JW*. Attenuated Glial Reactions and Photoreceptor Degeneration after Retinal Detachment in Mice Deficient in Glial Fibrillary Acidic Protein and Vimentin. (2007) Invest. Ophthalmol. Vis. Sci. 48, 2760-2768
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Takeda M, Takimiya A, Jiao J, Cho KS, Trevion SG, Matsuda T, and Chen DF. Alpha-aminoadipate induces Photoreceptor Regeneration and Progenitor Cell Properties of Muller Glia in Adult Mice. (2008) Invest Ophthalmol Vis Sci. 49,1142-1150.
Kameran Lashkari, M.D.
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Research Interests
With the increasing age of population of the U.S., the prevalence of age-related macular degeneration (AMD) is increasing in the U.S. population. We have concentrated our efforts in identifying biomarkers in the sera (blood) of patients with AMD. We have analyzed their sera for presence of various factors including pro-inflammatory cytokines and growth factors. We have identified several factors that may be associated with patients with AMD.
Our laboratory studies on AMD include tissue culture experiments to determine whether these factors are also released from ocular targets of AMD including retinal pigment epithelial cells as well as systemic sources. In collaboration with several medical centers, we are developing a local repository for AMD tissue. This tissue will be made available to researchers a the AMD center of excellence.
Publications
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Mo F, Prioia A, Johnson W, Lashkari K. Interferon-associated protein-10 and eotaxin are associated with age-related macular degeneration. (accepted, in revision)
(left)
Intermediate dry AMD. Paraffin-embedded section of an eye with intermediate dry AMD (AREDS 3), shows confluent drusen (arrow) between the Bruch's membrane (arrowhead) and the retinal pigment epithelial (**). The retinal pigment epithelium is elevated over the drusen and shows a "stressed" morphology.
Joan Stein-Streilein, Ph.D.
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Research Interests
Retinal Laser Burn is commonly used experimentally to stimulate neovascularization and create a model of AMD. In such studies little attention has been paid to the affects of RLB on the immune homeostasis of the eye. We recently published that RLB induces the loss of immune privilege (1, 2) in the contralateral eye as well as the burn eye(3). Studies are ongoing to discover the mechanisms that are affected by RLB and processes that might restore immune privilege. Restoration of immune privilege may be a novel therapy to treat AMD and prevent progression of damaging effects of inflammation that leads to vision loss.
Publications
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Sonoda, K.-H., M. Exley, S. Snapper, S. Balk, and J. Stein-Streilein. 1999. CD1 reactive NKT cells are required for development of systemic tolerance through an immune privileged site. J. Exp. Med. 190:1215-1225.
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Stein-Streilein, J. 2008. Immune regulation and the eye. Trends Immunol 29:503-586.
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Qiao, H., K. Lucas, and J. Stein-Streilein. 2009. Retinal laser burn disrupts immune privilege in the eye. Am J Pathol 174:414-422.
(left) Photomicrograph of paraffin-fixed slides stained with H&E of the retina of nontreated (WT) mice or RLB-treated mice. One day after laser treatment the Bruch’s membrane [choroid (CH),], retinal pigment epithelium (RPE), outer nuclear layer (ONL), and photoreceptor segment were damaged. RPEs are nonpigmented and appear to migrate toward the ONL (arrow) at 7 to 56 days after RLB. Small lumens (arrow) are evident in the subretinal space and choroidal vessels are dilated at 1 to 56 days after RLB. INL, internal nuclear layer; ONL, outer nuclear layer; RPE retinal pigment epithelium; CH, choroid. Original magnifications,X 400
Andrew W. Taylor, Ph.D.
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Research Interests
A key challenge in age-related macular degeneration (AMD) is the reconciliation of the genetic discovery of an AMD associated single nucleotide substitution in complement Factor H with an identifiable, pathogenic, phenotypic change in the molecule. Our project examines the possibility that key to drusen formation, and the associated pathologic sequelae of AMD is the condensation of proteins facilitated by mutant FH. The examination of the aggregative properties of mutant FH is a fundamentally novel theme in AMD research. We believe that AMD disease may be the result of protein condensation just as in the case of a number of other diseases such as cataracts, various amyloidoses including Alzheimer’s disease, and sickle cell disease. If so, slowing down the kinetics of such aggregation can be a promising strategy for delaying AMD beyond the normal life span.
Publications
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Zamiri P, Masli S, Kitaichi N, Taylor AW, and Streilein JW(deceased). Thrombospondin plays a vital role in the immune privileged eye. Invest. Ophthalmol. Vis. Sci. 2005; 46:908-919. (PMID: 15728547)
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Zamiri P, Masli S, Streilein JW, and Taylor AW. Pigment epithelial growth factor suppresses inflammation by modulating macrophage activation. Invest. Ophthalmol. Vis. Sci. 2006; 47: 3912-2918. (PMID: 16936104)
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Ng TF, Lavik E, Keino H, Taylor AW, Langer RS, Young MJ. Creating an immune-privileged site using retinal progenitor cells and biodegradable polymers. Stem Cells. 2007; 25:1552-1559. (PMID: 17548532)
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Ng TF, Kitaichi N and Taylor AW. In Vitro Generated Autoimmune Regulatory T Cells Enhance Intravitreous Allogeneic Retinal Graft Survival. Invest Ophthalmol Vis Sci. 2007; 48:5112-5117. (PMID: 17962463)
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Lau CH, and Taylor AW. The Immune Privileged Retina Mediates an Alternative Activation of J774A.1 Cells. Ocul. Immunol. Inflamm. 2009; In Press.

