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Tag: Macular Degeneration

  • Early Intervention is Critical to Saving Sight with Macular Degeneration

    Early Intervention is Critical to Saving Sight with Macular Degeneration

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    Newswise — Northampton, MA – [Feb 4, 2024] – Today, the American Macular Degeneration Foundation (AMDF) and the Thought Leadership & Innovation Foundation (TLI) announce a new strategic partnership aimed at amplifying awareness and understanding of macular degeneration, a leading cause of vision loss in older adults. 

    Kicking off this collaboration is the release of Living with Macular Degeneration: Patient Stories | Laura Carabello: The Benefits of Early Intervention, a short film produced by AMDF featuring TLI Fellow and AMDF patient advocate Laura Carabello. 

    “This strategic partnership with TLI unlocks a vast potential to reach millions impacted by macular degeneration,” says Matthew Levine, Director of Grants, Advocacy & Partnerships at AMDF. “TLI’s expertise in thought leadership amplification will strengthen our trusted resources, elevate patient voices, and drive impactful conversations with eye care specialists, researchers, and policymakers.”

    Carabello’s story offers a window into daily life with macular degeneration and the experience of anti-VEGF treatments. Diagnosed with wet macular degeneration, Laura credits her awareness of her genetic risk with seeking immediate medical attention upon experiencing symptoms, and thereby retaining much of her vision. Her narrative powerfully underscores the importance of early detection of macular degeneration and adherence to treatment plans.

    Macular degeneration, also known as age-related macular degeneration (AMD), affects central vision, color perception, and fine detail clarity, greatly impacting daily living and independence. Aging, family history, smoking, poor diet, obesity, and high blood pressure are key risk factors. 

    “This partnership embodies a shared commitment to making a tangible difference in the lives of those living with macular degeneration,” says Shawn Murphy, vice president, TLI. “Laura’s story is a powerful testament to the power of early intervention, ongoing care, and the transformative potential of effective treatments.”

    Together, AMDF and TLI are poised to illuminate a brighter path for individuals facing macular degeneration. Beginning in February, which is AMD Awareness Month, through ongoing collaborative efforts in awareness campaigns, groundbreaking research initiatives, and patient/provider support, they aim to minimize the impact of this condition and safeguard the precious gift of sight.

    About The American Macular Degeneration Foundation


    The American Macular Degeneration Foundation (macular.org) is a patient-centric foundation that supports potentially game-changing AMD research, education and advocacy in order to improve quality of life and treatment outcomes for all of those affected by AMD.

    About TLI


    The Thought Leadership & Innovation Foundation (TLI) is a not-for-profit organization that works at the nexus of science, technology and public health, innovating for superior prevention, treatment and outcomes for those facing life-altering medical diagnoses.TLI helps patients across the country and around the world find better healthcare outcomes. Visit www.thoughtfoundation.org and follow us on LinkedIn.



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    American Macular Degeneration Foundation (AMDF)

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  • Some mosquitoes like it hot

    Some mosquitoes like it hot

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    Newswise — Certain populations of mosquitoes are more heat tolerant and better equipped to survive heat waves than others, according to new research from Washington University in St. Louis.

    This is bad news in a world where vector-borne diseases are an increasingly global health concern. Most models that scientists use to estimate vector-borne disease risk currently assume that mosquito heat tolerances do not vary. As a result, these models may underestimate mosquitoes’ ability to spread diseases in a warming world.

    Researchers led by Katie M. Westby, a senior scientist at Tyson Research Center, Washington University’s environmental field station, conducted a new study that measured the critical thermal maximum (CTmax), an organism’s upper thermal tolerance limit, of eight populations of the globally invasive tiger mosquito, Aedes albopictus. The tiger mosquito is a known vector for many viruses including West Nile, chikungunya and dengue.

    “We found significant differences across populations for both adults and larvae, and these differences were more pronounced for adults,” Westby said. The new study is published Jan. 8 in Frontiers in Ecology and Evolution.

    Westby’s team sampled mosquitoes from eight different populations spanning four climate zones across the eastern United States, including mosquitoes from locations in New Orleans; St. Augustine, Fla.; Huntsville, Ala.; Stillwater, Okla.; St. Louis; Urbana, Ill.; College Park, Md.; and Allegheny County, Pa.

    The scientists collected eggs in the wild and raised larvae from the different geographic locations to adult stages in the lab, tending the mosquito populations separately as they continued to breed and grow. The scientists then used adults and larvae from subsequent generations of these captive-raised mosquitoes in trials to determine CTmax values, ramping up air and water temperatures at a rate of 1 degree Celsius per minute using established research protocols.

    The team then tested the relationship between climatic variables measured near each population source and the CTmax of adults and larvae. The scientists found significant differences among the mosquito populations.

    The differences did not appear to follow a simple latitudinal or temperature-dependent pattern, but there were some important trends. Mosquito populations from locations with higher precipitation had higher CTmax values. Overall, the results reveal that mean and maximum seasonal temperatures, relative humidity and annual precipitation may all be important climatic factors in determining CTmax.

    “Larvae had significantly higher thermal limits than adults, and this likely results from different selection pressures for terrestrial adults and aquatic larvae,” said Benjamin Orlinick, first author of the paper and a former undergraduate research fellow at Tyson Research Center. “It appears that adult Ae. albopictus are experiencing temperatures closer to their CTmax than larvae, possibly explaining why there are more differences among adult populations.”

    “The overall trend is for increased heat tolerance with increasing precipitation,” Westby said. “It could be that wetter climates allow mosquitoes to endure hotter temperatures due to decreases in desiccation, as humidity and temperature are known to interact and influence mosquito survival.”

    Little is known about how different vector populations, like those of this kind of mosquito, are adapted to their local climate, nor the potential for vectors to adapt to a rapidly changing climate. This study is one of the few to consider the upper limits of survivability in high temperatures — akin to heat waves — as opposed to the limits imposed by cold winters.

    “Standing genetic variation in heat tolerance is necessary for organisms to adapt to higher temperatures,” Westby said. “That’s why it was important for us to experimentally determine if this mosquito exhibits variation before we can begin to test how, or if, it will adapt to a warmer world.”

    Future research in the lab aims to determine the upper limits that mosquitoes will seek out hosts for blood meals in the field, where they spend the hottest parts of the day when temperatures get above those thresholds, and if they are already adapting to higher temperatures. “Determining this is key to understanding how climate change will impact disease transmission in the real world,” Westby said. “Mosquitoes in the wild experience fluctuating daily temperatures and humidity that we cannot fully replicate in the lab.”

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    Washington University in St. Louis

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  • Combining multiple maps reveal new genetic risk factors for blindness

    Combining multiple maps reveal new genetic risk factors for blindness

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    Newswise — Combining a map of gene regulatory sites with disease-associated loci has uncovered a new genetic risk factor of adult-onset macular degeneration (AMD), according to a new study publishing January 17th in the open access journal PLOS Biology by Ran Elkon and Ruth Ashery-Padan of Tel Aviv University, Israel, and colleagues. The finding advances the understanding of the leading cause of visual impairment in adults.

    AMD is caused by dysfunction in the retinal pigmented epithelium (RPE), a layer of tissue sandwiched between the photoreceptors that receive light, and the choriocapillaris, which nourishes the retina. Because of the central importance of the RPE in AMD, the authors began by exploring a transcription factor (a protein that regulates specific genes) called LHX2 which, based on the team’s analysis of mouse mutants, is central to RPE development. Knocking down LHX2 activity in RPE derived from human stem cells, they found that most affected genes were down-regulated, indicating that LHX2’s role was likely that of a transcriptional activator, binding to regulatory sites on the genome to increase activity of other genes.

    The authors found that one affected gene, called OTX2, collaborated with LHX2 to regulate many genes in the RPE. By mapping the genomic sites that OTX2 and LHX2 could bind to, they showed that 68% of those that bound LHX2 were also bound by OTX2 (864 sites in all), suggesting they likely work together to promote the activity of a large suite of genes involved in RPE development and function.

    A common method for finding genes that may contribute to a disease is to perform a genome-wide association study (GWAS), which identifies genome sequence differences between individuals (termed single nucleotide polymorphisms, or SNPs) that co-occur with disease. Numerous such studies have previously been done in AMD. However, a GWAS by itself cannot uncover a causal mechanism. Here, the authors compared their LHX2/OTX2 binding data to GWAS data in order to home in on variations that affected binding of the transcription factors, and thus may contribute to disease.

    One such binding site was located within the promoter region of a gene called TRPM1, which had been previously linked to AMD, and found that the sequence variant at that site altered the binding strength of LHX2; the so-called C version bound it more strongly than the T version, and activity of the TRPM1 gene was higher when the C allele was present instead of the T allele.

    The results of the study indicate that the previously known increased risk of AMD from the variant identified in the GWAS was due to reduction in binding of the LHX2 transcription factor to the TRPM1 gene promoter, with a consequent reduction in activity of this gene. The gene encodes a membrane ion channel, and previous studies have shown that mutations in the gene also cause visual impairment.

    “Our study exemplifies how delineation of tissue-specific transcriptional regulators, their binding sites across the genome, and their downstream gene-regulatory networks can provide insights into a complex disease’s pathology,” the authors said.

    Ashery-Padan adds, “The findings reveal a regulatory module consisting of LHX2 and OTX2 that controls the development and maintenance of the retinal pigmented epithelium, an important tissue of visual function. The genomic analyses further link the genomic regions bound by the two developmental factors to the genetics of the common, multifactorial blinding disease age-related macular degeneration (AMD).”

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    In your coverage, please use this URL to provide access to the freely available paper in PLOS Biologyhttp://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001924

    Press-only preview: https://plos.io/3GK3PF3

     

    Citation: Cohen-Gulkar M, David A, Messika-Gold N, Eshel M, Ovadia S, Zuk-Bar N, et al. (2023) The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration. PLoS Biol 21(1): e3001924https://doi.org/10.1371/journal.pbio.3001924

    Author Countries: Israel

    Funding: see manuscript

    Competing interests: The authors have declared that no competing interests exist.

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    PLOS

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