Age-related macular
degeneration (AMD) ...
is the leading cause of blindness in people over 65 years of age. In the United States alone, more than 70 million people are expected to have reached this age by the year 2050. Up to 20% of individuals older than 65 and 37% by age 75 are at risk for developing AMD. Read more
CALL FOR FUNDING APPLICATIONS:
ALERT:
The next submission date for IRRF regular grants is May 1, 2019.
Questions or request for information should be forwarded to Sandra Blackwood either by phone or email.
IRRF 2016 ANNUAL REPORT:
QUANTIFYING SPATIAL RELATIONSHIPS FROM WHOLE RETINAL IMAGES:
Bioinformatics, “Quantifying Spatial Relationships from Whole Retinal Images,” Brian E. Ruttenberg, Gabriel Luna, Geoffrey P. Lewis, Steven K. Fisher, and Ambuj K. Singh, NeuroscienceFOR ADDITIONAL INFORMATION OR OTHER INQUIRIES, PLEASE WRITE TO:
The International Retinal Research Foundation, Inc.
1720 University Boulevard
Birmingham, Alabama 35233
Attn: Sandra Blackwood, MPA
Executive Director
Phone: 205-325-8103
Fax: 205-325-8394
Or by email: sblackwood@irrfonline.org
Three awards are available at $35,000 each for one year for post doctoral scholars.
Submission Deadline is March 15, 2019.
RPB/IRRF Catalyst Award for Innovative Research Approaches for Age-Related Macular Degeneration (AMD) (SCROLL DOWN 
)
In 2014, the International Retinal Research Foundation (IRRF) accepted an invitation by Research to Prevent Blindness (RPB) to participate in a funding collaboration that would combine our collective resources to that of an anonymous donor and a generous bequest received from the Sybil Harrington Estate to RPB. It was requested that the funds be used for research that focused on stem cell research and AMD. The partnership made possible three grants at $250,000 over four years.
Realizing that there is an ongoing need for this type of funding partnership, RPB and IRRF came together again in 2017 to launch a second award, the RPB/IRRF Catalyst Award for Innovative Research Approaches for Age-Related Macular Degeneration, which provides funds to researchers who are working on novel approaches to AMD. Macular Degeneration is the leading cause of vision loss, affecting more than 10 million Americans – more than cataracts and glaucoma combined, and at present is considered an incurable eye disease. The specific factors that cause macular degeneration are not conclusively known, and research into this little understood disease is limited by insufficient funding. The RPB/IRRF Catalyst Awards are meant to act as seed money to high-risk/high-gain vision science research, which is innovative, cutting-edge and demonstrates out-of-the box thinking. Research related to both dry and wet forms of AMD are supported by this award.
The $300,000 grant is payable for up to 3 years upon approval of a 14-month substantive progress report, with further funding contingent upon satisfactory progress as judged by a well- respected peer reviewer.
In December 2017, after a rigorous scientific review process rooted in RPB review committees, two Catalyst Award winners were named:
(1) Dr. Catherine Bowes Rickman of Duke University School of Medicine, Associate Professor of Ophthalmology and Associate Professor in Cell Biology, whose research interest is the pathobiology of age-related macular degeneration. Her current studies involve the molecular mechanisms underlying the development of age-related macular degeneration, with a focus on development and studies of animal models of AMD, AMD pathogenesis and pre-clinical studies of novel therapies for AMD. Dr. Bowes Rickman has a strong track record of productive research in this field. For the Catalyst Award, she proposes to use unique and relevant models of chronic, dry AMD to test three therapeutic approaches that will shape strategies for targeting the complement pathway versus a combined therapeutic approach targeting both pathways. It is felt this project could have major implications in guiding future human clinical trials in this area.
(2) Debasish Sinha, PhD, University of Pittsburgh School of Medicine, is Professor of Ophthalmology and the recipient of a BrightFocus grant in 2016. Dr. Sinha also has an adjunct faculty appointment at Wilmer Eye Institute, Johns Hopkins. Dr. Sinha’s Catalyst Award proposal aims to develop a treatment for early, dry AMD that works by rejuvenating impaired lysosomal function. (Lysosomes act as the waste disposal system of the cell by digesting unwanted materials.) The committee felt this project is important and innovative because it attempts to target mechanisms that may underlie early stages of AMD – a critical unmet need. Dr. Sinha has exceptional experience in inflammation and, in particular, lysosomal biology, as well as access to high-level collaborators in this area.
Collaboration with Research to Prevent Blindness has been a very positive experience and the joining of our respective resources has allowed us to extend a significant award, and we feel confident that worthy recipients have been selected. Both IRRF and RPB are looking forward to seeing what these innovative individuals are able to accomplish with the grant money, which we hope will lead to a significant advance in AMD research. The importance of these awards cannot be overstated, since as already stated, there is currently no known cure for this disease. It is hoped this research will further our understanding of AMD and will lead to more options for treatment.
Collaborations That Provide Sustained Research Funding
Today’s vision scientists face many funding challenges making it imperative that all support options are available to them. Similarly, in order to ensure continued funding for young scientists who are developing their independent research projects, the IRRF must maximize every dollar. The formation of partnerships and collaborations with outstanding institutions has made it possible to accomplish this while producing a collective impact. Since 2013, New York-based Fight For Sight (FFS) and the IRRF have combined resources to provide an annual funding award: FFS – The International Retinal Research Foundation Grant-in-Aid Award that is offered and administered by FFS.
2017 — John T. Pena, MD, PhD, Weill Cornell Medical College for his work in diabetic retinopathy.
Grant Title: Human ocular fluid contains an intercellular communication system of endogenous exosomes.
Summary: The vitreous humor of the eye is a clear gel-like structure comprised of collagen and water and fills the back of the eye.
Traditional thinking has been that the vitreous is biologically inactive. Dr. Pena’s study showed a dense organized network of extracellular vesicles (EVs) in the human vitreous. However, attempts to image vitreous EVs in whole mount or tissue sections resulted in no evidence of EVs. Yet, electron microscope (EM) studies and nano-particle tracking analysis proved that millions of EVs exist in the vitreous. To solve this discrepancy and visualize the native anatomy of vitreous EVs a hypothesis emerged that the nanometer sized EVs were lost during tissue processing secondary to reversible formalin-fixation. Therefore, this team developed an innovative fixation technique to enable visualization of vitreous EVs in situ. In addition to identifying the vitreous EVs, it was proven that vitreous EVs are a highly potent vector that can be loaded with synthetic siRNAs or proteins, and subsequently transfects retinal cells in vitro and in vivo. The team has shown that vitreous EVs can be used as a vector to efficaciously deliver therapeutic recombinant proteins to tissues like the retina and choroid.
Current and Future Academic Plans: Dr. Pena’s academic plans are to continue to grow and become a productive physician-scientist. He is currently an Assistant Professor of Ophthalmology at Weill Cornell Medicine and Principal Investigator of the laboratory. Dr. Pena plans to use his training from the clinic and basic sciences to ask pertinent questions that remain a challenge in vision research. He hopes to provide straightforward solutions that can be translated to benefit his patients and will take the next few years as an opportunity to develop strong academic relationships with his mentors and students.
Dr. Greco obtained his PhD in physical chemistry at the University of Connecticut in 2015. Under the mentorship of Dr. Robert Birge, Dr. Greco’s graduate thesis work primarily involved the investigation of the structure and function of photoactive proteins, using both spectroscopic and quantum mechanical approaches. Much of his work has contributed towards the application of the protein bacteriorhodopsin into photonic and biomimetic devices, such as protein-based optical memories and processors, photovoltaic cells, and the retinal implant developed by LambdaVision, Inc. Concurrent with his work on bacteriorhodopsin, Dr. Greco has contributed to numerous computational analyses for the excited state of behavior of heterocyclic conjugated compounds, (e.g., porphyrin, chlorins, and corroles), carotenoids (e.g., peridinin), and other polyene-based chromophores rooted in biological systems. Dr. Greco has presented this work to international audiences and he continues to remain active in the field via several multidisciplinary collaborations. (Reprinted from Crunchbase: www.crunchbase.com/person/jordan-greco)
Since joining the research group of Dr. Robert Birge in 2009, University of Connecticut, Jordan Greco has been actively involved in the research and development that has led to the creation of the protein-based retinal implant and the commercialization of this technology through LambdaVision. (LambdaVision is led by University of Connecticut alumni and former students in Dr. Birge’s research group, Nicole Wagner, PhD and Jordan Greco, PhD.)
Dr. Greco’s graduate thesis work influenced the design and development of the retinal implant construct and the manufacturing techniques used to produce the prosthetic. As Chief Scientific Officer, Dr. Greco is responsible for manufacturing the retinal implants and establishing standard operating procedures and quality control measures. Moreover, his research efforts helped to direct critical proof-of-concept experiments that investigated the efficacy of the retinal implant architecture.
Recently, the company’s robotic system to manufacture films that could cure blindness was brought to the International Space Station U.S. National Laboratory by the SpaceX Dragon spacecraft.
On Earth, it takes LambdaVision approximately five days for each of its three robotic stations to produce an implant. The process involves a series of alternating dipping steps, which are subject to the effects of gravity. Once complete, the process results in a membrane approximately 60 um (micrometers) thick. A micrometer is one-millionth of a meter.
In the weightless conditions of the International Space Station, LambdaVision anticipates producing a more homogeneous and stable film. If successful, Wagner and Greco anticipate they can generate a similar signal with fewer layers of protein. This would drastically decrease the time for manufacturing, and save on the cost of materials.
IRRF News
EXPERIMENTAL EYE RESEARCH
Smc1 and the Cohesin Complex in Retinal Development and Disease: A New Mouse Model of Photoreceptor Degeneration
Rodrigo Martins, PhD.
Dr. Martins is an IRRF-Funded scientist at the Federal University of Rio de Janeiro, where he is an Assistant Professor. His funded project, Smc1 and the Cohesin Complex in Retinal Development and Disease: A New Mouse Model of Photoreceptor Degeneration, has resulted in a published paper in Developmental Biology, “N-myc regulates growth and fiber cell differentiation in lens development.”
Rodrigo Martins, PhD.
ABSTRACT:
Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. This study found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. The role of N-myc was examined in mouse lens development. Genetic inaction of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while “late” inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis.
TERMS: MYC – an immediate early response gene downstream of many ligand-membrane receptor complexes (Armelin et al., 1984; Kelly et al., 1983) binding to 10%-15% of genomic loci in mammals.
Oncogene – defined as a gene that encodes a protein that is capable of transforming cells in cultures or inducing cancer in animals.
Morphogenesis – can be defined as the processes that are responsible for producing the complex shapes of adults from the simple ball of cells that derives from division of the fertilized egg. (On-line Medical Dictionary, © 1997-98 Academic Medical Publishing & CancerWEB).
To read this paper in its entirety, please CLICK HERE.
Investigative Ophthalmology & Visual Science,
“The Role of Thrombin in Proliferative Vitreoretinopathy,”
Investigative Ophthalmology & Visual Science, “The Role of Thrombin in Proliferative Vitreoretinopathy,” Jeroen Bastiaans, Jan C. van Meurs, Verena C. Mulder, Nicole M.A. Nagtzaam, Marja Smits-te-Nijenhuis, Diana C. M. Dufour-van den Goorbergh, P. Martin van Hagan, Herbert Hooijkaas, and Willem A. Dik, Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. (July 2014, vol. 55, No. 7) This study was conducted with IRRF support – Willem A. Dik.
Proliferative vitreoretinopathy (PVR) is an inflammatory fibrotic disorder that can develop after rhegmatogenous retinal detachment, and is the most common failure of retinal detachment repair. Proliferative vitreoretinopathy development is characterized by the formation of subretinal, intraretinal, and/or epiretinal fibroproliferative membranes that cause the retina to detach due to the contractile properties of myofibroblasts that are abundantly present in these membranes. Retinal pigment epithelial (RPE) cells contribute to the formation of these fibroproliferative membranes through the secretion of cytokines and growth factors, proliferation, and dedifferentiation into extracellular matrix-producing myofibroblasts.
Current knowledge of the underlying pathobiological processes in PVR is still limited. Vitreous of patients with established proliferative vitreoretinopathy contains elevated levels of thrombin, which induces the production of proliferative vitreoretinopathy-associated cytokines, and growth factors by RPE. The purpose of this study is to determine the role of thrombin in the development of proliferative vitreoretinopathy (PVR).
To view the entire abstract CLICK HERE
Dr. Dik’s research group: Sita Virakul, Willem Dik, Jeroen Bastiaans, Nicole Nagtzaam, Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
UPDATE
Acetyl-11-keto-β-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy”
Although therapies directed toward vascular endothelial growth factor (VEGF) represent a significant step forward in the treatment of proliferative retinopathies, further improvements are needed. In the last few years, an intense research activity has focused around the use of herbal and traditional natural medicines as an alternative for slowing down the progression of proliferative retinopathies. In this study, the antiangiogenic effects of acetyl-11-keto-β-boswellic acid (AKBA), one of the active principles derived from the plant Boswellia serrata, used in Ayurvedic systems of medicine, was investigated. The team studied the antiangiogenic properties of AKBA using the mouse model of oxygen-induced retinopathy (OIR), which mimics the neovascular response seen in human retinopathy of prematurity. It was observed that AKBA reduced proliferation, migration and tube formation in human retinal microvascular endothelial cells (HRMECs) stimulated with exogenous VEGF, while it reduced migration and tube formation in untreated HRMECs. Taken together, the results demonstrate the antiangiogenic effects of AKBA in a model of pathologic neovascularization, providing a rationale for further investigation of AKBA as a promising therapeutic agent to reduce the impact of proliferative retinopathies.
Click Here to access this article.
Massimo Dal Monte, PhD, University of Pisa, Italy
Published Science: Experimental Eye Research, “Acetyl-11-keto-β-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy,” Matteo Lulli, Maurizio Cammalleri, Irene Fornaciari, Giovanni, Casini, Massimo Dal Monte. (April 2015, v 135, 67-80) This study was conducted with IRRF support – Dr. Massimo Dal Monte.
Eye site offers new insight on
age-related macular degeneration
This article was originally
published on the
November 12, 2015
By Megan Yeatts and Matt Windsor
Over the past 14 years, Christine A. Curcio, Ph.D. (pictured at right), a professor in the UAB School of Medicine’s Department of Ophthalmology, has collected images from hundreds of donor eyes in her search for the basic mechanisms underlying age-related macular degeneration. AMD is the leading cause of severe vision loss and legal blindness in Americans age 60 or older, affecting up to 15 million people in the United States today and almost 200 million people worldwide by 2020. As the population ages, those numbers will only increase. AMD occurs when the central portion of the retina, known as the macula, deteriorates. But the exact cause is unknown, and new treatments are desperately needed.
A few years ago, Curcio realized that the images and tissues she had collected, if properly annotated, classified, and made widely available, could prove invaluable to researchers and clinicians alike. It wasn’t as easy as uploading the photos to Facebook. The process took four years, and along the way, Curcio and her team, particularly research associate Jeffrey Messinger, DC, had to develop new naming systems to achieve the level of precision they were after. But the result, an open-access website known as Project MACULA (Maculopathy Unveiled by Laminar Analysis), has been a resounding success, leading to several notable discoveries that have advanced understanding of the disease.
SHARING KNOWLEDGE
At the close of the 2000s, a high-powered new technology called optical coherence tomography (OCT) was becoming widely available to practicing ophthalmologists. It can provide detailed cross-sectional views of all the layers of the retina and the blood vessels behind it. OCT was so powerful, Curcio said, that clinicians “were now able to see the same structures” as basic researchers with their tissue samples. Curcio recognized that high-quality, accurately annotated lab images of eyes with and without AMD could serve as an invaluable roadmap — helping clinicians interpret the patient images they were seeing with the new machines. “AMD is a degenerative disease that is laid out in delicate tissue layers, and if you know the microscopic histology, it is possible to see almost all of it in OCT,” Curcio said. Connecting the microscopic world with patient images from the clinic can lead to “better diagnoses, more efficient clinical trials for new treatments and eventually better experimental model systems to test new ideas,” she added.
A comparison of optical coherence tomography (OCT) and histology on the same eye allows Project MACULA users to identify the cells on a microscope image (bottom) that are responsible for the hyper-reflective spots seen in the OCT (top, red, yellow), plus examine the contents of drusen, AMD’s specific lesion (teal). “From this kind of analysis, we’ve learned that the retinal pigment epithelium is highly migratory in AMD,” Curcio said. “Finding out what these cells are doing is now a research priority, and with OCT, they can be observed in living people.”
Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization
Corson Lab Group. Timothy Corson front right.
Journal of Medicinal Chemistry. “Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization,” Helesha D. Basavarajappa, Bit Lee, Hyungjun Lee, Rania S. Sulaiman, Hongchan An, Carlos Magaña, Mehdi Shadmand, Alexandra Vayl, Gangaraju Rajashekhar, Eun-Yeong Kim, Young-Ger Suh, Kiho Lee, Seung-Yong Seo, and Timothy W. Corson. Department of Ophthalmology, Indiana University School of Medicine, Indianapolis. (June 2015, vol. 58) This study was conducted with IRRF support – Timothy W. Corson.
ABSTRACT
Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. The Corson Lab group undertook a cell-based structure-activity relationship study to develop more potent cremastranone analogues, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis and had efficacy in the oxygen-induced retinopathy model in vivo.
Dr. Corson was supported by IRRF for two years, 2014 - 2015. In addition to the above referenced paper, Synthesis and Mechanistic Studies of a Novel Homoisoflavanone Inhibitor of Endothelial Cell Growth, was published in 2014 in the journal Plos One. Also published in 2014 was, The first synthesis of the antiangiogenic homoisoflavanone, cremastranone, included in the journal Organic & Biomolecular Chemistry. Dr. Corson reported further findings of IRRF-supported work at the 2015 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).
To read more about Timothy Corson, PhD and the Corson Lab,
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
July 2017
Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration
Investigative Ophthalmology & Visual Science (IOVS),
Optical Coherence Tomography
Features Preceding the Onset of Advanced
Age-Related Macular Degeneration, Daniela Ferrara,
Rachel E. Silver, Ricardo N. Louzada, Eduardo
A. Novais, Gilian K. Collins, and Johanna M. Seddon.
Ophthalmic Epidemiology and Genetics
Service, Tufts Medical Center, 800 Washington
Street #450, Boston, MA 02111. USA. (July, 2017)
Invest Ophthalmol Vis Sci. 2017/58:3519-3529.
DOI:10.1167/iovs.17-21696
This study was conducted with IRRF support – Johanna Seddon.
PURPOSE:
Age-related macular degeneration (AMD) is a progressive disease with multifactorial etiology. There is a need to identify clinical features that are harbingers of advanced disease. Evaluations were conducted on morphologic features of the retina and choroid on optical coherence tomography (OCT) to determine if they predict progression to advanced disease.
CONCLUSION:
Abnormalities in the photoreceptors, retinal thickness, RPE, and choroid were associated with higher risk of developing advanced AMD. These findings provide insights into disease progression, and may be helpful to identify earlier endpoints for clinical studies.
To access this study: www.iovs.arvojournals.org/article.aspx?articleid=2644733
EXPERIMENTAL EYE RESEARCH
Astrocyte structural reactivity and
plasticity in models of retinal detachment
Experimental Eye Research, Astrocyte structural reactivity and plasticity in models of retinal detachment, Gabriel Luna, Patrick W. Keeley, Benjamin E. Reese, Kenneth A Linberg, Geoffrey P. Lewis, Steven K. Fisher. Neuroscience Research Institute, University of California, Santa Barbara; Center for Bio-image Informatics, University of California, Santa Barbara. (March 2016) This study was conducted with IRRF support – Geoffrey Lewis and Steven Fisher.
Drs. Geoffrey Lewis and Steven Fisher and Gabriel Luna, BA, Research Specialist with the Neuroscience Research Institute.
ABSTRACT:
Although retinal neurodegenerative conditions such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and retinal detachment have different etiologies and patho-logical characteristics, they also have many responses in common at the cellular level, including neural and glial remodeling. Structural changes in Müller cells, the large radial glia of the retina in retinal disease and injury have been well described, that of the retinal astrocytes remains less so. Using modern imaging technology to describe the structural remodeling of retinal astrocytes after retinal detachment is the focus of this paper. We present both a review of critical literature as well as novel work focusing on the responses of astrocytes following rhegmatogenous and serous retinal detachment. The mouse presents a convenient model system in which to study astrocyte reactivity since the Müller cell response is muted in comparison to other species thereby allowing better visualization of the astrocytes. We also show data from rat, cat, squirrel, and human retina demonstrating similarities and differences across species. Our data from immunolabeling and dye-filling experiments demonstrate previously undescribed morphological characteristics of normal astrocytes and changes induced by detachment. Astrocytes not only upregulate GFAP, but structurally remodel, becoming increasingly irregular in appearance, and often penetrating deep into neural retina. Understanding these responses, their consequences, and what drives them may prove to be an important component in improving visual outcome in a variety of therapeutic situations. Our data further supports the concept that astrocytes are important players in the retina’s overall response to injury and disease.
To access this article, please CLICK HERE.
Smc1 and the Cohesin Complex in Retinal Development and Disease
Investigative Ophthalmology & Visual Science, “The Role of Thrombin in Proliferative Vitreoretinopathy”
Acetyl-11-keto-β-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy
UPDATE
Eye site offers new insight on age-related macular degeneration
Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization
Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration
Astrocyte structural reactivity and plasticity in models of retinal detachment
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Contact us
For additional information or other inquiries, please write to:
The International Retinal Research Foundation, Inc.
1720 University Boulevard
Birmingham, Alabama 35233
Attn: Sandra Blackwood, MPA, Executive Director
Phone: 205-325-8103
Fax: 205-325-8394
Or by email: sblackwood@irrfonline.org
