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 IRRF will accept applications for Postdoctoral Scholar Awards for 2018. Three Awards are available at $35,000 each for one year. Submission Deadline is March 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
Lasker/IRRF Initiative News
The IRRF will not be accepting applications for regular grants in 2018. The next submission date is May 1, 2019.
MAY 23, 2017 IN IRRF INITIATIVE
Astrocytes and Glaucomatous Neurodegeneration
A longitudinal section of a DBA 2J mouse, a widely used mouse model of glaucoma, optic nerve head including adjacent retina. Image courtesy of Keun-Young Kim and Mark Ellisman (National Center for Microscopy and Imaging Research, San Diego).
The first report of the IRRF Initiative, Astrocytes and Glaucomatous Neurodegeneration, was published in November 2010. Since then, significant scientific progress has occurred in the field. It now is commonly accepted that astrocytes are a critical element of glaucoma pathophysiology, and new animal models have moved the field considerably. In 2014, the Initiative’s Joint Advisory Board agreed to evaluate the current state of research in the field. In March 2015, more than 40 scientists from all over the world met at the Howard Hughes Medical Institute Janelia Research Campus in Ashburn, Virginia. They identified questions, topics and experiments that should be addressed within the next five years.
The results have been summarized in five review articles published in a special issue of Experimental Eye Research (Astrocytes and Glaucoma, Volume 157, pp. 1-38, April 2017).
Glaucoma remains the second leading cause of blindness in the United States, surpassed only by severe cataracts. The need for a way to prevent glaucoma is great, and the Lasker/IRRF Initiative hopes that the two meetings it has sponsored on glaucoma move us closer to the day when this disease can be prevented.
APRIL 20, 2017 IN IRRF INITIATIVE
Amblyopia: Challenges and Opportunities
A longitudinal section of a DBA 2J mouse, a widely used mouse model of glaucoma, optic nerve head including adjacent retina. Image courtesy of Keun-Young Kim and Mark Ellisman (National Center for Microscopy and Imaging Research, San Diego).
Amblyopia, often called ‘lazy eye’, is a reduction of visual acuity occurring despite a normal structural eye. Risk factors include deprivation that may be caused by congenital cataract or ptosis (drooping upper eyelid), anisometropia (asymmetric refractive error between the two eyes), or strabismus (misaligned eyes). Failure to diagnose and effectively treat the condition can lead to permanent visual deficits. The cost of amblyopia is enormous; in addition to visual deficits, patients with amblyopia have double the lifetime risk of total blindness, with the consequent limitations on career choices and challenges to independence.
The Lasker/IRRF Initiative examined the significant scientific challenges confronting investigators working on amblyopia and developed a number of proposals to accelerate the discovery of new insights and innovative approaches to better diagnose, treat, and even prevent amblyopia using multidisciplinary scientific, technological and engineering approaches.
A hard copy of the report is available by request to sblackwood@irrfonline.org.
JAN. 7, 2015 IN IRRF INITIATIVE
Restoring Vision to the Blind
Image produced by the Gamm Laboratory, University of Wisconsin School of Medicine and Public Health.Degenerative diseases of the retina are devastating conditions leading to severe visual impairment and blindness; their causes and paths of treatment have long evaded scientists. Since 2008, the Lasker Foundation and the IRRF have been engaged in a collaborative effort to accelerate discovery of sight-saving treatments and ways to prevent retinal degenerative diseases. Chaired by John Dowling of Harvard University, the Initiative has produced two reports — information and downloads are available from the links below — that identify knowledge gaps in research and apply innovative solutions to retinal diseases.
A hard copy of the report is available by request to sblackwood@irrfonline.org.
The Lasker/IRRF Initiative has now completed its examination of rapidly developing cutting-edge technologies that can be applied to reestablish light sensitivity and visual perception to the blind. Leaders in retinal degeneration, ocular genetics, electrophysiology and sensorimotor research, molecular biology, neuro-ophthalmology, nanotechnology and regenerative medicine, ophthalmic imaging, and other disciplines relevant to the project met over the past two years. During this time, they identified key impediments to research progress and developed novel ideas for new studies, particularly creative collaborations, which surmount technical obstacles and accelerate research advances. Their consensus recommendations are the basis for the Initiative's latest summary report, "Restoring Vision to the Blind," which identifies innovative approaches to accelerate research to restore visual function lost by retinal degenerative diseases.
So enormous are the challenges of restoring retinal function, so immense are the ramifications for those now living without sight, and so exciting is the research being conducted worldwide to conquer blindness that, in addition to the Initiative's own print version of the summary report, the Association for Research in Vision and Ophthalmology (ARVO), asked to publish it as a special issue of its online journal Translational Vision Science & Technology. The journal is listed in PubMed (Trans. Vis. Sci. Tech.: December 2014, Vol. 3, No. 7) and is open access, so the report will be readily accessible to a global audience.
This report was created as part of the IRRF Initiative.
MARCH 24, 2012 IN IRRF INITIATIVE
Diabetic Retinopathy: A Path to Progress
The Lasker/IRRF Initiative's second report ("Diabetic Retinopathy: A Path to Progress"), released in 2012, addresses diabetic retinopathy, the most common and most serious of the ocular complications of diabetes mellitus. In the US alone, the most recent (2007) estimate from the Centers for Disease Control and Prevention indicated that some 23.6 million individuals, 7.8 percent of the entire US population, have diabetes. Of these, nearly 30 percent have retinopathy, and an estimated 4.4 percent, or about one million individuals, have advanced, vision-threatening retinopathy. A very large proportion of these are from minority populations. Although the best data come from the US, the problem is global. Moreover, diabetic retinopathy afflicts people with both type 1 and type 2 diabetes; because the incidence of type 2 diabetes is rising, due at least in part to the worldwide increase in obesity, diabetic retinopathy is a growing concern.
A hard copy of the report is available by request to sblackwood@irrfonline.org.
Since it was first described in the nineteenth century, diabetic retinopathy has been considered a disease of the retinal blood vessels. However, a variety of highly sensitive techniques that have recently been developed suggest that much earlier anatomic, biochemical, and physiologic abnormalities in the neuronal and glial cells of the retina precede these vascular lesions, and lead to the question of whether these are true predecessors of the vascular disorder and may be appropriately called "preclinical" diabetic retinopathy. Research conducted during the past half century has demonstrated unequivocally that control of blood glucose to near-normal levels reduces the incidence and progression of retinopathy and other complications in both types of diabetes. Additional evidence indicates that mechanisms other than hyperglycemia also affect the development of diabetic retinopathy, including classical genetic influences. Finally, unique features of the retina may be responsible for its high susceptibility to complications of diabetes.
These observations from past basic and clinical investigations serve as a backdrop for the Lasker/IRRF Initiative on Diabetic Retinopathy. The investigation of this disease included two 2011 workshops of experts in a wide range of scientific disciplines, at which the complex links between the rise in blood glucose levels and changes in neuronal/glial function and vascular changes that eventually can destroy vision in an eye were explored. From these discussions, the group identified nine specific areas for further scrutiny:
- Early signs of diabetic retinopathy
- Role of glucose, lipids, and oxygen in diabetic retinopathy
- Diagnostic methods
- Genetics and environmental susceptibility
- Epidemiology and unusual cohorts
- Present and proposed approaches to therapeutics
- Pathogenesis of diabetic retinopathy
- Vascular and retinal repair
- Animal models
At a plenary session of all workshop participants, held in March 2012, scientists examined these targeted areas, pinpointed key research hurdles that impede research progress, and developed a series of innovative proposals for new research, using novel approaches and cutting edge technologies. The report "Diabetic Retinopathy: What We Know and A Path to Progress," published in November 2012, summarizes the findings of the Initiative. It provides a path to new ideas and experiments that will increase our understanding of this disease and lead to the development of effective therapies for preventing this devastating disease.
This report was created as part of the IRRF Initiative.
OCT. 14, 2010 IN IRRF INITIATIVE
Astrocytes and Glaucomatous Neurodegeneration
The August 2009 workshop of the Initiative's Astrocytes and Glaucomatous Neurodegeneration. Credit: Milos PeknyGlaucoma is often called the sneak thief of vision because it can develop without obvious symptoms. Whereas certain risk factors are apparent — high intraocular pressure and age — exactly how these risk factors contribute to the disease is by no means clear.
The first program of the Lasker/IRRF's Initiative for Innovation in Vision Science, launched in 2009, explored the dual role of astrocytes in glaucoma. Astrocytes are cells that perform many functions to maintain healthy optic nerve tissue but have also been implicated in playing a negative role in glaucomatous degenerative disease.
A hard copy of the report is available by request to sblackwood@irrfonline.org.
The Initiative convened two workshops with experts in diseases of the retina and glaucoma, as well as bench and clinical scientists with expertise in a number of complementary fields,whose combined skills, knowledge, and experience could point the way toward an understanding and eventual cure of this disease. Participants identified and refined the main unsolved questions, as well as important areas for further glaucoma research that may now be experimentally addressed using modern techniques.
In March 2010, workshop participants and other scientists with expertise that could fill additional knowledge gaps met and outlined a plan of potential studies to surmount hurdles that have hindered progress in this field. "Astrocytes and Glaucomatous Neurodegeneration," a report published by the Initiative in November 2010, summarizes this comprehensive examination of how astrocytes function in health and disease. The report also articulates the challenges to better understanding how astrocytes may play a key role in glaucoma and outlines innovative approaches that could advance new methods to diagnose, treat, and even prevent this devastating and intractable disease.
In addition to mapping ways to understand the role of astrocytes in glaucoma and neurodegenerative disease, the report serves as an important platform on which to launch new collaborative research efforts to further our understanding and response to not only glaucoma, but a myriad of other poorly understood conditions.
This report was created as part of the IRRF Initiative.
Astrocytes and Glaucomatous Neurodegeneration
The Lasker/IRRF Initiative for Innovation in Vision Science
Amblyopia: Challenges and Opportunities
The Lasker/IRRF Initiative for Innovation in Vision Science
Restoring Vision to the Blind
The Lasker/IRRF Initiative for Innovation in Vision Science
Diabetic Retinopathy:
A path to progress
The Lasker/IRRF Initiative for Innovation in Vision Science
Astrocytes and Glaucomatous Neurodegeneration
The Lasker/IRRF Initiative for Innovation in Vision Science
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.
Other 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,
EXPERIMENTAL EYE RESEARCH
June 22, 2016
Improved cell metabolism prolongs photoreceptor survival upon retina-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy
Oncotarget, Improved cell metabolism prolongs photoreceptor survival upon retina-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy, Marina Zieger and Claudio Punzo, Department of Ophthalmology and Gene Therapy Center, University of Massachusetts Medical Center, Worcester, MA. This study was conducted with IRRF support.
ABSTRACT:
Age-related macular degeneration (AMD) is characterized by malfunction and loss of retinal-pigmented epithelium (RPE) cells. Because the RPE transfers nutrients from the choriocapillaris to photoreceptor (PR), PRs are affected as well. Geographic atrophy (GA) is an advanced form of AMD characterized by severe vision impairment due to RPE loss over large areas. Currently, there is no treatment to delay the degeneration of nutrient deprived PRs once RPE cells die. Here we show that cell-autonomous activation of the key regulator of cell metabolism, the kinase mammalian target of rapamycin complex 1 (mTOR1), delays PR death in the sodium iodate induced model of RPE atrophy. Consistent with this finding loss of mTORC1 in cones accelerates cone death as cones fail to balance demand with supply. Interestingly, promoting rod survival does not promote cone survival in this model of RPE atrophy as both, rods and cones suffer from a sick and dying RPE. The findings suggest that activation of metabolic genes downstream of mTORC1 can serve as a strategy to prolong PR survival when RPE cells malfunction or die.
To read this paper in its entirety, please CLICK HERE.
To visit the Punzo Lab website, please CLICK HERE.
Left: Dr. Claudio Punzo (middle) and his staff. Marina Zieger is pictured far left.
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
Improved cell metabolism prolongs photoreceptor survival...
Astrocyte structural reactivity and plasticity in models of retinal detachment
Current Research News
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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
