Month: July 2013

Veterinary ophthalmology researchers from the University of Pennsylvania have used gene therapy to restore retinal cone function and day vision in two canine models of congenital achromatopsia, also called rod monochromacy or total color blindness.

Achromatopsia is a rare autosomal recessive disorder with an estimated prevalence in human beings of about 1 in 30,000 to 50,000. It primarily affects the function of the cone photoreceptors in the retina and serves as a representative model for other more common inherited retinal disorders affecting cones. Cone function is essential for color vision, central visual acuity and most daily visual activities, which underlines the importance of the newly developed treatment.

The treatment cured younger canines regardless of the mutation that caused their achromatopsia. It was effective for the 33 months of the study and most likely is permanent; however, researchers also observed a reproducible reduction in the cone therapy success rate in dogs treated at 54 weeks of age or older.

The successful therapy in dogs was documented by the restoration of the cone function using electroretinography and by objective measure of day vision behavior. The behavioral results suggest that inner retinal cells and central visual pathways were able to usefully process the input from the recovered cones.

The results represent the second successful cone-directed gene replacement therapy in achromatopsia animal models and the first outside of mouse models. The gene therapy targets mutations of the CNGB3 gene, the most common cause of achromatopsia in humans. Achromatopsia-affected dogs represent the only natural large animal model of CNGB3-achromatopsia.

The results hold promise for future clinical trials of cone-directed gene therapy in achromatopsia and other cone-specific disorders.

“The successful restoration of visual function with recombinant adeno-associated virus-mediated gene replacement therapy has ushered in a new era of retinal therapeutics,” said Andr??s M. Kom??romy, assistant professor of ophthalmology at the Penn School of Veterinary Medicine and lead author of the study.

Many vision-impairing disorders in humans result from genetic defects, and, to date, mutations have been identified in -150 genes out of – 200 mapped retinal disease loci. This wealth of genetic information has provided fundamental understanding of the multiple and specialized roles played by photo-receptors and the retinal pigment epithelium in the visual process and how mutations in these genes result in disease. Together with the development of gene-transfer technologies, it is now possible to realistically consider the use of gene therapy to treat these previously untreatable disorders.

The article, available online in advance of its publication in the journal Human Molecular Genetics, was conducted by Kom??romy, Jessica S. Rowlan and Gustavo D. Aguirre of the Department of Clinical Studies at Penn Vet; Monique M. Garcia, Asli Kaya and Jacqueline C. Tanaka of Temple University; John J. Alexander of the University of Florida and the University of Alabama; Vince A. Chiodo and William W. Hauswirth of the University of Florida; and Gregory M. Acland of Cornell University.

Research was supported by the National Eye Institute of the National Institutes of Health, the Foundation Fighting Blindness, the Macula Vision Research Foundation, the McCabe Fund, the ONCE International Prize, the Van Sloun Fund for Canine Genetic Research, Hope for Vision and Brittany Rockefeller and family.

Hauswirth and the University of Florida have a financial interest in the use of rAAV therapies and own equity in Applied Genetic Technologies Corp., a company that may commercialize some aspects of this work. The University of Pennsylvania, the University of Florida and Cornell University hold a patent on the described gene-therapy technology.

Source:
Jordan Reese
University of Pennsylvania

The first global consensus report on meibomian gland dysfunction – a major cause of lid disease and evaporative dry eye – has been published in a special issue of the Investigative Ophthalmology & Visual Science (IOVS) journal. The report is the result of findings from a two-year-long workshop composed of more than 50 leading clinical and basic research experts from around the world.

The workshop participants used an evidence-based approach to develop a worldwide definition: meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease.

Using the same methodology, the participants developed a universal classification system – based on pathophysiology, rather than anatomical changes or the severity of disease – to meet the needs of clinicians and researchers alike. The consensus paper further proposes recommendations for diagnosing MGD and MGD-related disorders and presents a sequence of diagnostic tests to be performed in an order that will minimize the extent to which one test influences those that follow.

Also included in the report are recommendations for the evaluation and grading of the severity of MGD, management of and therapy for the disease and norms for clinical trials designed to evaluate pharmaceutical interventions for treatment.

The International Workshop on Meibomian Gland Dysfunction was conducted by the Tear Film & Ocular Surface Society (TFOS). While the breadth and depth of the consensus findings are expected to have a far-reaching impact on the clinical care of patients, the group of experts concur that additional research be conducted to further study other aspects of MGD. These include its association with dry eye disease and standardized and validated ways to identify symptoms and signs of MGD.

Source:
Katrina Norfleet
Association for Research in Vision and Ophthalmology

A protein long thought to be one of the body’s supporting players has quietly been taking a lead role in healthy eyesight, a discovery that could rapidly lead to treatments for babies born before their eyes are finished growing, University of Florida and Harvard Medical School researchers have found.

The finding, described in separate, back-to-back papers published in the June 19 Proceedings of the National Academy of Sciences, offers a new target for therapies for retinopathy of prematurity, a potentially blinding disease that annually affects about 15,000 babies.

In newborns with the disease, oxygen-starved areas of the retina compensate by quickly growing new blood vessels. But these new vessels are fragile and leaky.

“We’ve identified a protein that is part of the body’s natural defenses in oxygen-deprived conditions,” said Maria B. Grant, M.D., a professor of pharmacology and therapeutics at UF’s College of Medicine. “When babies are born before levels of this protein are normal, blood vessels spread abnormally throughout the retina. But if we can increase the protein to more normal levels in premature babies, it should result in healthier blood vessel growth.”

The protein – insulin-like growth factor binding protein-3, or IGFBP-3 – was thought to exist exclusively to regulate insulin-like growth factor-1, a molecular growth factor that is necessary for the development of nerve, muscle, bone, liver, kidney, lung, eye and other body tissues.

But in studies of mice and of human cells in cultures, scientists from the Program in Stem Cell Biology and Regenerative Medicine at UF’s McKnight Brain Institute found that IGFBP-3 activates stem cells and other reparative cells of the bone marrow and the lining of blood vessels.

Researchers from Harvard Medical School and the University of Goteborg in Sweden arrive at essentially the same conclusion in PNAS, identifying the protein IGFBP-3 as a promising therapeutic agent after analyzing data from mouse and human studies.

“This discovery has a big future in helping premature babies,” said Alexander V. Ljubimov, Ph.D., a professor of medicine at UCLA and director of Ophthalmology Research Laboratories at Cedars-Sinai Medical Center. “The idea is to administer this already clinically available protein to premature babies to stabilize the existing vessels in the retina, prevent their loss and block the compensatory growth of new, aberrant vessels. Finding the right dose may enable babies to cope with the first phases of their life without becoming blind.”

Retinopathy of prematurity affects infants weighing less than 2.75 pounds who are born within the first 31 weeks of pregnancy, according to the National Eye Institute. More than 1,000 require medical treatment and about 500 become legally blind.

Treatments based on IGFBP-3 could advance relatively quickly because it is a natural protein and presumably safe, Ljubimov said.

“The discovery has added credibility because independent research groups took different approaches to show essentially the same thing,” said Ljubimov, who was not involved in the research. “There is independent confirmation from totally different research teams within the same journal.”

At UF, researchers infused IGFBP-3 into one eye of each of nine mice before placing the animals into a high-oxygen chamber for five days. When scientists compared vascular growth within the retinas, they found blood vessels were closer to normal in eyes treated with IGFBP-3.

When UF scientists repeated the experiment in 18 mice treated with bone marrow stem cells expressing IGFBP-3, they found the treated eyes developed normally.

In addition to studies in mice, Harvard research collaborators in Sweden examined infants with retinopathy of prematurity in a prospective clinical study and found that the IGFBP-3 levels were lower than those of healthy infants, further suggesting that the protein helps prevent oxygen-induced blood vessel loss and promotes healthy vascular regrowth.

“The implications for retinopathy are that IGFBP-3 appears to have benefit in preventing vessel loss independent of insulin-like growth factor-1 in both the mouse model of oxygen-induced retinopathy and in infants with retinopathy of prematurity,” said Lois E.H. Smith, M.D., Ph.D., an associate professor of ophthalmology at Harvard Medical School and senior author of the Harvard study. “Supplementation to increase IGFBP-3 in premature infants at risk for ROP to normal levels in utero may prove beneficial in this disease.

“Harvard Medical School researchers and collaborators at the University of Goteborg are currently conducting a phase 1 clinical study to evaluate the use of IGFBP-3 in combination with IGF-1 to examine the effects on prevention of retinopathy in premature infants, based on the clinical findings in our study,” Smith said. “This work suggests that both IGF-1 and IGFBP-3 acting independently help prevent retinopathy.”

Contact: John Pastor

University of Florida

Individuals age 49 and older with cataract and those age 49 to 74 years with age-related macular degeneration appear to have higher mortality rates over an 11-year period than those without such visual impairments, according to a report in the July issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Several studies have shown associations between visual problems and the risk of death in older individuals, according to background information in the article. “The mechanisms for higher mortality associated with visual impairment remain unclear,” the authors write. “It could be attributed to age-related ocular conditions, such as age-related macular degeneration (ARMD) or cataract, which can be markers of biological aging. Alternatively, visual impairment and its related ocular conditions could share a similar pathogenesis with other conditions associated with increased mortality.”

Sudha Cugati, M.S., of the University of Sydney, Australia, and colleagues assessed 3,654 individuals age 49 and older who were part of the Blue Mountains Eye Study, an ongoing examination of visual disorders in the Blue Mountains area west of Sydney. When the participants enrolled in the study, between 1992 and 1994, they were assessed for overall visual impairment and its two main causes: cataract, a disease in which the eye’s lens is covered by a film that reduces sight, and ARMD, which occurs when the macula, the area at the back of the retina that produces the sharpest vision, deteriorates over time.

By Dec. 31, 2003 — an average of 11 years of follow-up — 1,051 participants (28.9 percent) died. Rates of death were higher among those with any visual impairment than among those without (54 percent vs. 34 percent), among those with ARMD than those without (45.8 percent vs. 33.7 percent) and among those with cataract than those without (39.2 percent vs. 29.5 percent).

“After adjusting for factors that predict mortality, neither visual impairment nor ARMD was significantly associated with all-cause mortality in all ages,” the authors write. “Among persons younger than 75 years, however, ARMD predicted higher all-cause mortality.” Among participants of all ages, having cataract also was associated with a higher risk of death from any cause.

It remains unclear whether there is a direct or indirect link between visual impairment and death or if another factor not measured in this study affected the results, the authors note. “The implications of these findings also remain uncertain: whether such an association indicates that visual impairment, age-related eye disease or both are markers of aging and frailty or whether these ocular conditions accelerate aging, thus leading to relatively earlier death in older persons,” they conclude. “If a direct or indirect causal effect from visual impairment on earlier death is confirmed, regular assessment of vision in older persons may lead to early detection, facilitating treatments that could reduce the impact of visual impairment.”

(Arch Ophthalmol. 2007;125(7):917-924)

This study was supported by grants from the Australian National Health and Medical Research Council. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Source: Jie Jin Wang

JAMA and Archives Journals

Applied Genetic Technologies Corporation (AGTC), a privately-held, clinical stage biotechnology company developing novel systems to deliver human therapeutics, announces that AGTC has entered into an agreement with the National Neurovision Research Institute (NNRI), the clinical trial support organization for the Foundation Fighting Blindness(FFB), to collaborate in experiments using the AAV delivery system in the treatment of two genetic retinal diseases known to cause blindness at an early age. The research will be coordinated by AGTC and will be conducted at The University of Florida, Oregon Health & Science University, The University of Pennsylvania, and The University of British Columbia.

The collaboration will focus on development of treatments for two of the more common genetic retinal diseases that cause blindness at a very early age: X-Linked Retinoschisis (XLRS) and Achromatopsia. “We are delighted to expand our strong relationship with the FFB and the NNRI through this collaboration,” said Sue Washer, President and CEO of AGTC. “We continue to be encouraged by the data supporting the AAV vector system’s ability to provide sustained delivery and expression of therapeutic levels of many different biologics in the eye with minimal observable toxicity to date in either animal or human testing. There are hundreds of thousands of patients suffering from retinal diseases who currently have no treatment options and this research collaboration is another step towards using the AAV delivery system to address this unmet need and improve the patients’ quality of life.”

“This collaboration is a tremendous boost for the development of gene therapy products for retinal degenerative diseases and NNRI’s partnership with AGTC accelerates these emerging treatments into and through the clinical trial process,” said Stephen Rose, Ph.D., Chief Research Officer, Foundation Fighting Blindness. “It affirms the great potential for science guided foundations and academic researchers to work in partnership with commercial firms like AGTC that have the commitment and experience to bring these promising treatments directly to patients.”

XLRS is an inherited form of retinal degeneration affecting young boys. Patients present with poor vision either in infancy or at school age. Visual acuity usually worsens during the teenage years and then stabilizes until complicated by vitreous hemorrhage or retinal detachment during adulthood. There is no treatment available for the retinal degeneration in XLRS, which affects approximately 34,000 patients in the US and Europe. Previous research has shown promising signs of efficacy in mouse models and this collaboration will explore safety and efficacy in primates.

Achromatopsia is an inherited condition that presents at birth with impaired visual acuity, lack of color discrimination and extreme light sensitivity resulting in daytime blindness. There is no specific treatment for Achromatopsia, although deep red tinted spectacles or contact lenses can reduce symptoms of light sensitivity. Approximately 22,000 patients in the US and Europe suffer from this disease. Previous research has shown promising signs of efficacy in dog models and this collaboration will enable expanded safety and efficacy studies.

About AGTC

AGTC is focused on the research and development of novel therapeutics for patients with unmet medical needs utilizing AGTC’s proprietary, non-pathogenic adeno-associated virus (AAV) delivery system. AGTC has demonstrated that this system can be used to deliver a normal form of a gene in both animals and humans thus allowing their own body to produce sustained therapeutic levels of important biologics. The Company’s most advanced programs in development are treatments for Alpha-1 antitrypsin deficiency, a disease causing a progressive loss of lung function, and Leber’s Congenital Amaurosis, an inherited condition causing early blindness. Both utilize AGTC’s proprietary AAV system and production methods. AGTC has licensed a significant portion of its intellectual property from the University of Florida where researchers originated this ground-breaking work and has received significant financing from some of the world’s leading venture capital firms: InterWest Partners, Intersouth Partners and MedImmune Ventures. For more information see agtc.

Source
Foundation Fighting Blindness (FFB)
National Neurovision Research Institute

“More than in any preceding year,” says Glaucoma Research Foundation (GRF) President and CEO Thomas M. Brunner, “there is a heightened sense of anticipation around the annual Research Overview by the four principal investigators of the GRF-funded Catalyst For a Cure (CFC) research consortium that opens GRF’s 31st Anniversary Benefit and Celebration at 5 pm, Wednesday, January 28, 2009, in San Francisco’s legendary Palace Hotel.

“As the conventional understanding of glaucoma evolves from being described as an eye disease to a neurodegenerative disease,” Brunner reports, “there is an emerging sense that glaucoma could actually be the first neurodegenerative disease we can cure. And that extraordinary possibility will be an overriding theme of all the presentations, I’m sure.”

The Research Overview is co-chaired by noted Silicon Valley philanthropists and entrepreneurs, Nobuko Saito Cleary and Gary Cleary PharmD, PhD. The Overview is followed at 6 pm by The President’s Reception and presentation of The President’s Award to Rohit Varma, MD, (Doheny Eye Center, University of Southern California), for his definitive studies revealing Latino community at highest risk for glaucoma.

GRF’s highest honor, The Catalyst Award, will be presented to American Academy of Ophthalmology Executive Vice President H. Dunbar Hoskins Jr, MD, at the dinner following at 7 pm. Presenting The Catalyst Award will be the 31st Anniversary Celebration national chair, William Tasman, MD (Wilmer Eye Institute, University of Pennsylvania).

Catalyst For A Cure: A New Model For Scientific Research

Established by GRF in 2000, the CFC was first proposed as a partnership by the Steven and Michele Kirsch Foundation on the premise that the search for a cure should be a priority, and that the pace of discovery could be accelerated with important innovations: instead of the traditional academic approach of sole scientists working in isolation, the project would bring together investigators with complementary skills working together in a genuine, real time collaboration, and recognizing that traditional ophthalmic approaches to glaucoma research were well served, we would recruit for the research team, instead, from the burgeoning world of neuroscience and genetics.

CFC Principal investigators include: David Calkins PhD, Vanderbilt University; Philip Horner PhD, University of Washington; Nicholas Marsh-Armstrong PhD, Johns Hopkins University; and Monica Vetter PhD, University of Utah. Now in its third and final three-year cycle, major funding for CFC is provided by a grant to GRF from the (insert Barr language here).

“Our CFC’s research breakthroughs from the year just ending continue to make strides both in understanding what causes glaucoma, and in conducting studies that translate the basic science into potential glaucoma treatments,” Brunner said. He cited:

– Two interventional studies that firmly establish that oxidative stress is a factor in the rate of loss of cellular function from glaucoma – effectively preventing vision loss in a relevant model of glaucoma. Results of these studies were published this year in the scientific journal Investigative Ophthalmology and Visual Science and reported at the annual meeting of the Association for Research in Vision and Ophthalmology.

– In another important pair of studies, the CFC discovered that the cell death that causes vision loss in glaucoma has two distinct phases, and that axonal degeneration precedes neuronal loss. These facts point to a therapeutic window for interventions. Importantly, the studies have determined that vision loss from glaucoma can be predicted by observing changes specific to genes and proteins. The CFC published both of these findings in the highly regarded Journal of Neuroscience.

Glaucoma Research In Broader National Context

“This year we also benefited from two major activities that give us a much broader national context in which to evaluate recent findings as well as set CFC goals for the year ahead.”

The first event was a major summit meeting of internationally renowned scientists and physicians recently convened with GRF funding by David Calkins PhD at Vanderbilt University. “Unlike the current indirect glaucoma treatments that work to lower the pressure within the eye,” Dr. Calkins said, “the goal of this meeting was to discover ways to cure the disease by stopping and possibly reversing damage to the optic nerve itself. Of particular interest are the similarities between glaucoma and other chronic neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Lou Gehrig’s disease. The hope is that by studying the mechanisms of neurodegeneration, new targets for novel therapeutic interventions before the critical point of irreversible damage occurs.”

Second, GRF’s new Director of Scientific Programs and Licensing, Allen Poirson PhD, completed GRF’s first Glaucoma Research Status (GRS) survey, evaluating current research areas of interest, as well as funding priorities from national pace setters. “Finding a cure or therapies that can avert this threat,” reports Dr. Poirson, “is simply not an urgent national imperative. We looked at several basic indicators and documented in the government sector the low priority standing for funding new glaucoma research at the National Eye Institute and the resulting small amount of new research this low standing makes possible. In the corporate sector, there are no new ‘Mechanisms of Action’ medications in Phase 3 trials.” In fact, said Poirson, the handful of foundations like GRF in the non-profit sector funding glaucoma research provided approximately the same amount of funding for new research programs utilizing molecular and cellular biology techniques that emphasize neurodegeneration and neuroprotection pathways as did the NEI in the last two years: just $4 million!

About The Glaucoma Research Foundation

Located in San Francisco and now celebrating its 31st Anniversary year, GRF is the nation’s most experienced foundation dedicated solely to glaucoma research and education. In addition to funding innovative research like the Catalyst For a Cure research consortium and its Shaffer Grants for Innovative Glaucoma Research, GRF also is the “go to” agency for education materials, including the definitive reference for newly diagnosed, Understanding and Living with Glaucoma (available in both English and Spanish editions); a special brochure serving those at highest risk, including African-Americans, Latinos, and children; and a toll free phone line, 800-826-6693, staffed during office hours with an information specialist to handle a variety of inquiries.

For more information about GRF, call 800.826.6693. For information about tickets for the 31st Anniversary Benefit and Celebration, contact Carmen Torres (ctorresglaucoma, 415.986.3162).

Glaucoma Research Foundation

Potentially blinding blood vessel growth in the cornea resulting from eye injury or even surgery can be reduced by more than 50 percent with a new manmade protein, researchers say.

“We believe eventually we’ll be able to use this protein to help patients in many situations where blood vessel formation is detrimental, including cancer, diabetic retinopathy and macular degeneration,” says Dr. Balamurali K. Ambati, corneal specialist at the Medical College of Georgia and Augusta Veterans Affairs Medical Center. Dr. Ambati is corresponding author of the study published in the November issue of Investigative Ophthalmology & Visual Science.

The body can produce new blood vessels to promote healing after trauma, such as a corneal transplant, a significant corneal scratch from a contact lens or retinal oxygen deprivation caused by diabetes or aging. This natural response, called angiogenesis, becomes detrimental when new growth obstructs vision or when a tumor pirates the process to survive.

In an animal model, researchers used the protein they developed to reverse obstructive growth as long as one month after injury, says Dr. Ambati. That’s a very long time after injury in a mouse’s lifetime, indicating even well-established blood vessels are susceptible to intraceptor-mediated regression, he says.

This intraceptor traps vascular endothelial growth factor, or VEGF, inside the protein making machinery of a cell. It’s made with a portion of a VEGF receptor called sflt-1, a free-floating receptor recently shown to help keep the cornea clear by taking up and effectively neutralizing VEGF. Although other molecules have an anti-angiogenic effect, sflt-1 was the only one they found that spurs corneal blood vessels when blocked. The work, published in October in Nature, was led by teams at MCG and the University of Kentucky.

“Now we have designed a novel recombinant molecule where we take a subunit of sflt-1 and couple it with a four-amino-acid peptide tail,” he says. “The tail essentially handcuffs the manmade molecule within the protein-making machinery of the cell so that it stays there and anything that binds with it, namely VEGF, stays there too. So it’s a very specific way of down-regulating a target protein.”

In May 2005, Dr. Ambati and his colleagues published work in Investigative Ophthalmology & Visual Science showing the intraceptor helped reduce blood vessel development in the test tube and animal models for corneal injury and melanoma.

“Now we are talking about making them go away,” says Dr. Ambati. While the work is still in the laboratory, it provides further evidence of the intraceptor’s potential clinical application, he says.

The work shows the intraceptor prompts regression of blood vessels by inducing programmed cell death, or apoptosis, in the vascular endothelial cells that line the vessels.

“The biology of all this is showing this molecule interrupts the proper folding of proteins involved in existing blood vessels, which makes them die. It’s a nice result,” says Dr. Ambati.

Some existing anti-angiogenesis treatments target VEGF outside cells. “It is important to bind it within cells because certain cells, such as cancer and blood vessel cells, have the capability to produce their own VEGF and their own receptors,” Dr. Ambati says. “Imagine trying to block from the outside a factory that has everything it needs inside. You have to throw a monkey wrench inside the factory and that is what we managed to do.”

For the study, the manmade protein was injected directly into the cornea with a microneedle. “Ideally we would like to develop a topical eye drop with a long-term delivery system,” says Dr. Ambati.

His research team is pursuing its work of the intraceptor’s potential role in destroying blood vessels that help sustain cancers. They also are looking at a biodegradable polymer cage so they can encapsulate the intraceptor, tag it with a homing device for target cells and deliver it “like a missile carrying a payload” into the desired cells where it will slowly release the intraceptor, he says.

Co-authors include Dr. Nirbhai Singh, MCG postdoctoral fellow; Pooja D. Jani and Shivan Amin, MCG medical students; and Tushar Suthar, a medical student at New York Medical College in Valhalla.

The research was funded by the Knights-Templar Eye Foundation, Fight For Sight Grant-in-Aid and the Association for Research in Vision and Ophthalmology/Alcon Postdoctoral Fellowship.

Contact: Toni Baker

Medical College of Georgia

A team of researchers led by Dr. Jayakrishna Ambati at the University of Kentucky has discovered a biological marker for neovascular age-related macular degeneration (AMD), the leading cause of blindness in older adults.

The marker, a receptor known as CCR3, shows strong potential as a means for both the early detection of the disease and for preventive treatment. The findings were reported in an article published online Sunday by the prestigious journal Nature.

“This is a major paradigm shift in macular degeneration research,” said Ambati, a professor of physiology, professor and vice-chair of ophthalmology and visual sciences, and the Dr. E. Vernon and Eloise C. Smith Endowed Chair in Macular Degeneration at the UK College of Medicine. “With CCR3, we have for the first time found a unique molecular signature for the disease. This brings us closer than we have ever been to developing a clinical diagnostic tool to discover and treat the disease early, before vision is lost.”

Neovascular (or “wet-type”) macular degeneration is caused by choroidal neovascularization (CNV) – the invasive growth of new blood vessels in the thin vascular layer that provides nourishment and oxygen to the eye. Central vision loss occurs when these abnormal blood vessels invade the retina, the light-sensitive tissue that lines the inner surface of the eyeball.

“Once the vessels invade the retina, the horse has already left the barn,” Ambati said. “At that point, drugs can slow the process, but irreparable damage has often already been done. This is why finding a means for early detection and intervention is so important.”

Drs. Atsunobu Takeda, Judit Z. Baffi, Mark E. Kleinman, Won Gil Cho and other researchers in the Ambati laboratory discovered that CCR3 – a molecule also implicated in inflammatory processes – is expressed on the surface of CNV vessels in humans but is absent from normal vascular tissue.

“CCR3 chemokine receptor is known to be a key player in the allergic inflammation process, but Dr. Ambati’s studies have now identified CCR3 as a key marker of the CNV process involved in AMD. If researchers can determine why CCR3 is expressed in the CNV of AMD patients, they could further understand AMD disease progression,” said Dr. Grace L. Shen, director of the ocular immunology and inflammation program at the National Eye Institute.

Ambati’s research team was able to detect these same abnormal blood vessels in the living eyes of mice by attaching anti-CCR3 antibodies to tiny semiconductor nanocrystals called “quantum dots” and injecting these into the mice. The antibodies cause the quantum dots to attach to CCR3 on the surface of the abnormal blood vessels, making them visible with conventional ocular angiography techniques, even before they have penetrated the retina. This was not possible before.

“This is an exciting discovery for the millions of people at risk of developing wet macular degeneration, because this new imaging technology introduces the possibility of detecting pathological neovascularization before retinal damage and vision loss occur,” said Dr. Stephen J. Ryan, professor of ophthalmology at the University of Southern California and member of the National Academy of Sciences’ Institute of Medicine.

The research team discovered that CCR3 not only provides a unique signature for CNV, but the gene actively promotes the growth of these abnormal blood vessels in the eye. Thus the same anti-CCR3 antibodies used to detect CNV could potentially be useful as a clinical treatment to prevent macular degeneration.

The early results look promising. Treatment with anti-CCR3 antibodies reduced CNV in mice by about 70 percent, as opposed to 60 percent with VEGF-based treatments currently in clinical use. Ambati says Phase I clinical trials are not far off.

“The identification of CCR3 on the endothelial cells of CNV in human AMD is a major breakthrough,” said Dr. Patricia A. D’Amore, professor of ophthalmology at Harvard Medical School. “The preclinical data is very exciting and suggests that targeting CCR3 may be the basis of the next generation of targeted anti-angiogenesis therapy for wet AMD.”

Ambati’s paper, “CCR3 is a target for age-related macular degeneration diagnosis and therapy,” was released online today and will be printed in an upcoming issue of Nature.
Age-related macular degeneration is the leading cause of blindness in older adults in the industrialized world, affecting some 10-12 million people in the United States – more than all cancers combined and about twice as many as Alzheimer’s disease. Nationwide, about 250,000 new cases of CNV are reported annually.

This work was supported by research grants from the National Eye Institute of the National Institutes of Health and an unrestricted grant from Research to Prevent Blindness. Dr. Ambati is also supported by a Doris Duke Distinguished Clinical Scientist Award and the Burroughs Wellcome Translational Research Clinical Scientist Award. Key collaborators in the study include Drs. Marc Rothenberg (Cincinnati Children’s Hospital), M. Elizabeth Hartnett (UNC-Chapel Hill), Craig Gerard (Children’s Hospital, Boston), Salvatore Grisanti (University of Luebeck), and Justine Smith (Casey Eye Institute).

Source
National Eye Institute

“The incidence of individuals with a mathematics learning disability is between 6 – 7% of the population.” Since there are more than 300 million individuals in the United States, up to 21 million men, women, and children may be affected by this disorder. Sidney Groffman OD, MA, FCOVD, Professor Emeritus at SUNY College of Optometry, author of the article published in the December 2009 issue of Optometry & Vision Development, also says, “This is unfortunate because math skills are of prime importance in everyday life enabling us to understand number concepts and do calculations. Math ability is essential for many occupations and professions.”

Dr. Dominck Maino, editor of Optometry & Vision Development says that in this article, “Dr. Groffman goes on to review a particular ability called subitizing. This is a basic skill which has been known to be a precursor of math skills.” Dr. Groffman has helped to develop a subitizing vision therapy computer program that has been designed and based upon theories and experimental data appropriate for improving math skills. It consists of a diagnostic test and four therapy programs. This paper reviews subitizing and how members of the College of Optometrists in Vision Development can use this computer program to help their patients.

In this same issue of Optometry & Vision Development, Drs. Burkhart Fischer and Klaus Hartnegg of the Centre of Neuroscience, Optomotor Laboratory, of the University of Freiburg, present their research on instability of fixation and children with dyslexia. They note that “Dyslexic subjects have higher incidence of fixation instabilities as compared with their corresponding age group. The percentage of affected subjects was 25% for the binocular instability independent of age. Daily practice improves binocular fixation by 55%, with simple stability improving by 19%. To the extent that the binocular vision instability causes dynamic problems of stereo-vision (3D vision), the trained subjects have less and shorter periods of double images arriving at cortical levels of visual processing. This in turn makes it easier for them to identify letters and short sequences of letters with the result of fewer problems in reading.”

And finally, researchers at Western University of Health Sciences, College of Optometry, the Jules Stein Eye Institute, UCLA, and the Southern California College of Optometry, Drs. Chris Chase, Chinatsu Tosha, Eric Borsting, and William Ridder have noted that the Conlon survey is a useful tool to identify students with near work vision problems that negatively affect academic/school performance or are associated with eye focusing problems.

About Optometry & Vision Development

Optometry & Vision Development (OVD) is a peer-reviewed open access journal indexed in the online Directory of Open Access Journals.

About COVD

The College of Optometrists in Vision Development (COVD) is an international, non-profit optometric membership organization that provides education, evaluation, and board certification programs in behavioral and developmental vision care, optometric vision therapy, and visual rehabilitation. The organization is comprised of doctors of optometry, vision therapists and other vision specialists.

Source: College of Optometrists in Vision Development

For the first time, a study combines measurements of abnormalities in the eye with models for assessing how well an individual can see, meaning it may be possible to program a machine to automatically produce prescriptions for corrective lenses.

The model for predicting visual clarity – based on measurements taken by today’s highly accurate aberrometers – could also enable surgeons to more accurately assess and correct the vision of patients undergoing lasik or refractive surgery.

New technology in aberrometers means ophthalmologists and others can accurately measure refractive error and other abnormalities in the eye’s optics. But these instruments cannot use these measurements to predict visual acuity, or how well a person can actually see. Usually, ophthalmologists and optometrists rely on a patient’s ability to identify characters on an eye chart to determine visual clarity.

A study recently published in the online, peer-reviewed Journal of Vision (journalofvision/8/4/17), published by the Association for Research in Vision and Ophthalmology (ARVO) evaluates the performance of several simple metrics that predict visual acuity from wavefront aberrations – the eye measurements provided by an aberrometer.

To do so, authors Andrew B Watson and Albert J. Ahumada Jr (both of NASA Ames Research Center, CA) make a clear distinction between a metric and model.

“A metric is a formula that describes a quantitative relationship,” explains Watson. “It is accurate but not necessarily adaptable to different situations. A model is a mechanistic description that explains why a relationship exists. If the parameters of a model change, one can make predictions of how an outcome will change.”

The authors developed a model that successfully predicts visual acuity using both wavefront aberrations and simulations of the complex task of identifying individual letters from the widely used Sloan letter set. They then designed a simple metric that performs as well as the more elaborate model.

The metric could be used internationally. Explains Watson: “The same metric, because of its generality, can predict acuity measured with other symbol sets, such as Chinese characters.

“With this metric, the aberrometer will be able to give direct predictions of visual acuity, and could also provide an automatic optimal refractive prescription for the patient.”

ARVO is the largest eye and vision research organization in the world. Members include more than 12,500 eye and vision researchers from over 70 countries. The Association encourages and assists research, training, publication and dissemination of knowledge in vision and ophthalmology. For more information, visit arvo/.

Source: Joanne Olson

Association for Research in Vision and Ophthalmology