SPOTLIGHT ON RESEARCH ARCHIVE

Lasker/IRRF Investigator Exchange Funds Awarded

Mon, 9 Jan 2012 07:56:17 -0600

In 2009, The Lasker/IRRF Initiative for Innovation in Vision Science was established to encourage collaborations for significant advances toward finding a cure or solution for vision loss due to retinal disease. The first topic undertaken by the Initiative was astrocytes and glaucomatous neurodegeneration with preliminary sessions in Woods Hole, Massachusetts culminating in a conclusive session at the Janelia Farm Research Campus of the Howard Hughes Medical Institute in March 2010.
Resulting from these meetings was the allotment of additional funds to enable Dr. Rudolf Fuchshofer, Institute of Anatomy at the University Regensburg, Germany, to spend two months in 2011 in the laboratories of Dr. Harry A. Quigley, Director, Glaucoma Service and Dana Center for Preventive Ophthalmology at Wilmer Eye Institute, Johns Hopkins University in Baltimore, Maryland, USA. Dr. Fuchshofer trained to analyze the optic nerve using a special software program, Metamorph Image Analysis, designed for histological analysis and which allows a semi-automatic quantification of axons within the optic nerve. He also learned to analyze the loss of retinal ganglion cells (RGC) on whole mounts of the retina.
Dr. Fuchshofer was sponsored by Dr. Ernst Tamm at the University Regensburg Institute of Human Anatomy & Embryology, who presented the topic, Norrin Initiates Signal Cascade in Müller Glia That Protects Retinal Ganglion Cells From Excitoxic Damage, at the March 2010 session of the Lasker/IRRF Initiative.

Effect of Aging on Photoreceptor Function, Alexander V. Kolesnikov, Jie Fan, Rosalie K. Crouch, and Vladimir J. Kefalov.

Wed, 2 Mar 2011 09:14:57 -0600

As people age, their visual acuity, night vision, dark adaptation, and contrast sensitivity deteriorate. This decline results partly from loss of rods, but other processes underlying these phenotypes are poorly understood. To determine whether age-related vision loss in mice is similar to that in humans, photoreceptor electrophysiology, morphology and photopigment levels in old and young mice were compared. Like in humans, visual acuity and contrast sensitivity under bright light were maintained in old mice, indicating that cone function was unimpaired, whereas both measures deteriorated under dim light, indicating rod dysfunction. The number of photoreceptors and the length and width of rod outer segments decreased with age, and responses to light were correspondingly reduced. Increased variance in dark current (reflecting the number of cGMP channels open at rest) in surviving rods accounted for most of their reduced sensitivity. Unlike in humans, however, dark adaptation was unimpaired in old mice; likewise, the visual cycle was unaffected by aging. (Reprinted from The Journal of Neuroscience by permission of the authors.)

New Research Reveals Unexpected Biological Pathway in Glaucoma

Thu, 17 Feb 2011 12:39:36 -0600

The Lasker Foundation and the International Retinal Research Foundation challenged scientists who participated in the 2009 Woods Hole Workshops and the 2010 Janelia Farm sessions to collaborate on a pertinent glaucoma issue with the encouragement of funding from the International Retinal Research Foundation up to $100,000 for one year. Mark H. Ellisman, MA, PhD, Director of the Center for Research in Biological Systems at the University of California San Diego, and Nicholas Marsh-Armstrong, PhD, Assistant Professor at the Johns Hopkins University School of Medicine at Kennedy Krieger submitted a proposal that was subsequently approved for funding. The IRRF funds, combined with those of the National Eye Institute of the National Institutes of Health, became additional funding for a study principally supported by the Melza M. and Frank Theodore Barr Foundation through the Glaucoma Research Foundation.
The result has been exciting and productive. The study published in the Proceedings of the National Academy of Sciences identified a new and unexpected biological pathway that appears to contribute to the development of glaucoma and its resulting vision loss. Prior research suggested that the optic nerve head, the point where the cables that carry information from the eye to the brain first exit the eye, plays a role in glaucoma. Researchers also report a series of findings that offer novel insights into cellular and molecular mechanisms operating at the optic nerve head in two mouse models of glaucoma. Most notably, they discovered that at a specific location within the optic nerve head, there is a unique class of cells called astrocytes that demonstrate properties that appear to make them a critical factor in the visual blinding that occurs in glaucoma.
Researchers found abnormal forms of a protein called gamma synuclein that is similar to abnormal forms of alpha synuclein, a related protein known for its key role in cell loss in Parkinson’s disease. This suggests a biological process similar to Parkinson’s disease unfolds in glaucoma at the specific anatomical location pinpointed in this study for the first time.
Also discovered at this anatomical location is a surprising process whereby astrocytes remove the debris of neurons, the cells that die in neurodegenerative disorders such as glaucoma. It is likely that this newly discovered process involving removal of the debris of one cell by a neighboring cell is important in glaucoma and Parkinson’s disease, as well as for many neurodegenerative diseases. (Synopsis reprinted from EurekAlert!) www.eurekalert.org/pub_releases/2001

Link in the Cause of Vision Loss in Macular Degeneration, Diabetic Retinopathy, and other Retinal Diseases Found

Fri, 1 Jan 2010 11:31:00 -0600

“Immune cells called macrophages and the cytokine interleukin-10 spur the development of the damaging blood vessels,” reports Rajendra S. Apte, MD, PhD (above left), a Washington University retinal specialist. (Cytokines, such as interleukin-10 (IL-10) are small proteins that regulate immunity and inflammation.) “The offending immune system cell and cytokine are identical.” Apte, an assistant professor of ophthalmology and visual sciences and of developmental biology, previously found in mice that IL-10 contributes to abnormal blood vessel growth by interacting with macrophages in the eye, leading to growth beneath the mouse retina. This correlates to what happens in patients who have the “wet” form of macular degeneration.
In diabetic retinopathy, new vessels also form and contribute to vision loss. One difference is that those vessels do not develop beneath the retina, but grow into the retina. A similar condition, retinopathy of prematurity, occurs when premature babies with immature retinas experience an obstruction in blood flow into the retina called ischemia. In response, these children often develop abnormal blood vessels in the retina that can cause retinal detachment and interfere with vision.
“The mechanisms inducing angiogenesis may not be exactly the same in a premature baby and a 70-year-old person,” says Ape, “but it’s important to note that the two key players – macrophages and interleukin-10 – appear to be the prime movers in this process of damaging blood vessel formation in all of these potentially blinding diseases.” It is his belief that therapies that interfere with the IL-10/macrophage pathway might help prevent vision loss.
Members of the scientific team for this study included first author Dru S. Dace, PhD, (above right) recipient of the 2008 Alston Callahan, MD Postdoctoral Scholar Award; Aslam A. Kahn, PhD, recipient of the 2009 Alston Callahan, MD Postdoctoral Scholar Award; and Rajendra S. Apte, MD, PhD, IRRF-funded principal investigator.