Breaking News
December 13, 2018 - Targeting biochemical pathway may lead to new therapies for alleviating symptoms of anxiety disorders
December 13, 2018 - FDA Approves Tolsura (SUBA®-itraconazole capsules) for the Treatment of Certain Fungal Infections
December 13, 2018 - Are scientists studying the wrong kind of mice?
December 13, 2018 - Computer memory: A scientific team builds a virtual model of a key brain region
December 13, 2018 - Visual inspection alone is insufficient to diagnose skin cancer
December 13, 2018 - Paternal grandfather’s access to food associated with grandson’s mortality risk
December 13, 2018 - Our brain senses angry voices in a flash, study shows
December 13, 2018 - PM2.5 Exposure Linked to Asthma Rescue Medication Use
December 13, 2018 - Can’t exercise? A hot bath may help improve inflammation, metabolism, study suggests
December 13, 2018 - Can artificial intelligence help doctors with the human side of medicine?
December 13, 2018 - Virginia Tech and UC San Diego researchers team up to develop nonopioid drug for chronic pain
December 13, 2018 - NIH offers support for HIV care and prevention research in the southern United States
December 12, 2018 - Activating brain region could revive the urge to socialize among opioid addicts
December 12, 2018 - Relationship impairment appears to interfere with seeking mental health treatment in men
December 12, 2018 - Sleep, Don’t Cram, Before Finals for Better Grades
December 12, 2018 - Effective treatments for urticarial vasculitis
December 12, 2018 - Gun violence is a public health issue: One physician’s story
December 12, 2018 - The Science of Healthy Aging
December 12, 2018 - Yes to yoghurt and cheese: New improved Mediterranean diet
December 12, 2018 - Researchers uncover a number of previously unknown insecticide resistance mechanisms
December 12, 2018 - Regulating the immune system’s ‘regulator’
December 12, 2018 - In breaking bad news, the comfort of silence
December 12, 2018 - Study finds upward link between alcohol consumption and physical activity in college students
December 12, 2018 - FDA issues warning letter to Zhejiang Huahai Pharmaceutical involved in valsartan recall
December 12, 2018 - Weight history at ages 20 and 40 could help predict patients’ future risk of heart failure
December 12, 2018 - Presence of antiphospholipid antibodies tied to first-time MI
December 12, 2018 - DNA analysis finds that stethoscopes are teaming with bacteria
December 12, 2018 - New study could help inform research on preventing falls
December 12, 2018 - Women and men with heart attack symptoms receive different care from EMS
December 12, 2018 - Disrupted biological clock can contribute to onset of diseases, USC study shows
December 12, 2018 - New publications generate controversy over the value of reducing salt consumption in populations
December 12, 2018 - New data from TAILORx trial confirms lack of chemo benefit regardless of race or ethnicity
December 12, 2018 - Specific class of biomarkers can accurately indicate the severity of cancer
December 12, 2018 - Meds Taken Do Not Vary With ADL Impairment in Heart Failure
December 12, 2018 - Long-term study shows that HIV-2 is deadlier than previously thought
December 12, 2018 - People living near oil and gas wells show early signs of cardiovascular disease
December 12, 2018 - IONTAS founder and pioneer in phage display technology attends Nobel Prize Award Ceremony
December 12, 2018 - People who eat red meat have high levels of chemical associated with heart disease, study finds
December 12, 2018 - New method uses water molecules to unlock neurons’ secrets
December 12, 2018 - Genetics study offers hope for new acne treatment
December 12, 2018 - New computer model predicts prostate cancer progression
December 12, 2018 - Nobel Laureates lecture about immune checkpoint therapy for cancer treatment
December 12, 2018 - More Illnesses From Tainted Romaine Lettuce Reported
December 12, 2018 - Aspirin could reduce HIV infections in women
December 12, 2018 - The EORTC Brain Tumor Group and Protagen AG collaborate to study immuno-competence of long-term glioblastoma survivors
December 12, 2018 - Insights into magnetotactic bacteria could guide development of biological nanorobots
December 12, 2018 - Sacrificial immune cells alert body to infection
December 12, 2018 - Low-salt diet may be more beneficial for females than males
December 12, 2018 - Major soil organic matter compound battles chronic wasting disease
December 12, 2018 - Findings may open up new ways to treat dwarfism and other ER-stress-related conditions
December 12, 2018 - New computational model provides clearer picture of shape-changing cells’ structure and mechanics
December 12, 2018 - 10 Facts on Patient Safety
December 12, 2018 - Poorest dying nearly 10 years younger than the rich in ‘deeply worrying’ trend for UK
December 12, 2018 - Innovative care model for children with ASD reduces use of behavioral drugs in ED
December 12, 2018 - Spending time in and around Hong Kong’s waters linked to better health and wellbeing
December 12, 2018 - Simple measures to prevent weight gain over Christmas
December 12, 2018 - Research advances offer hope for patient-tailored AML treatment
December 12, 2018 - Researchers discover a ‘blind spot’ in atomic force microscopy
December 12, 2018 - Sprayable gel could help prevent recurrences of cancer after surgery
December 12, 2018 - SLU researchers explore how fetal exposure to inflammation can alter immunity in newborns
December 12, 2018 - How do patients want to discuss symptoms with clinicians?
December 12, 2018 - Zinc chelation may be able to deliver drug to insulin-producing cells
December 12, 2018 - Brigham researchers develop automated, low-cost tool to predict a woman’s ovulation
December 12, 2018 - Some people with Type 2 diabetes may be testing their blood sugar more often than needed
December 12, 2018 - Slow-growing type of glioma may be vulnerable to immunotherapy, suggests study
December 12, 2018 - Study provides new information regarding microRNA function in cellular homeostasis of zebrafish
December 12, 2018 - Study provides new understanding of mysterious ‘hereditary swelling’
December 12, 2018 - Researchers shed new light on how to combat Shiga and ricin toxins
December 12, 2018 - Pregnant Women Commonly Refuse Vaccines
December 12, 2018 - Drug treatment could offer new hope for some patients with brain bleeding
December 12, 2018 - Health care financial burden of animal-related injuries is growing, study says
December 12, 2018 - Macrophage cells could help repair the heart following a heart attack, study finds
December 12, 2018 - Researchers develop new system for efficiently producing human norovirus
December 12, 2018 - New artificial intelligence-based system to differentiate between different types of cancer cells
December 11, 2018 - Brazilian professors propose guidelines for therapeutic use of melatonin
December 11, 2018 - Healthy Lifestyle Lowers Odds of Breast Cancer’s Return
December 11, 2018 - New research identifies two genes linked to serious congenital heart condition
December 11, 2018 - NIH Director talks science, STEM careers with preteens
December 11, 2018 - Disabling a Cellular Antivirus System Could Improve Gene Therapy
December 11, 2018 - New tool swiftly provides accurate measure of patients’ cognitive difficulties
INSiGHT identifies unique retinal regulatory genes

INSiGHT identifies unique retinal regulatory genes

image_pdfDownload PDFimage_print
Dr. Melanie Samuel Credit: Baylor College of Medicine

Vision begins in the retina, a light-sensing neural network in the eye that is critical for our ability observe the world around us. Researches at Baylor College of Medicine, Texas Children’s Hospital and the Hospital for Sick Children have developed a new platform that enables them to uncover new regulators of retina neurons. This platform, named INSiGHT, was used to examine more than 100 genes, and 16 key retinal regulatory genes were identified.

Of these genes, 15 have not been previously identified as retinal regulators and nine have been associated with human diseases. The findings, which are published in the journal Cell Reports, contribute to a more complete picture of the genetic factors involved in retinal function in health and disease.

“Unless we can understand the molecular pathways that control neural fate, identity and connectivity, it becomes difficult to prevent or treat visual impairments, which globally affect 253 million people,” said corresponding author Dr. Melanie Samuel, assistant professor of neuroscience and in the Huffington Center on Aging at Baylor College of Medicine.

Motivated by the larger goal of better understanding the molecular control of the nervous system, Samuel and her colleagues focused on the retina.

“We study the retina for many reasons. First, people are visually oriented. In fact, a large part of our brain is dedicated to visual processing,” said Samuel, who also is part of Baylor’s Dan L Duncan Comprehensive Cancer Center. “Second, the retina is a simpler part of the nervous system relative to the brain, making it more tractable to study. In addition, we know a great deal about the retina, including the characteristics of its many neuron types and their basic connectivity. Finally, the retina can provide a window into the brain since molecules and principles that govern one system often also affect the other. “

INSiGHT

In this study, Samuel and her colleagues took an unbiased approach to screen for new genes involved in the normal development of the retina. They partnered with the Knockout Mouse Project at Baylor College of Medicine led by Dr. Arthur Beaudet, professor of molecular and human genetics, and Dr. Mary Dickinson, professor of molecular physiology and biophysics, who are co-authors of the study.

“The project, which is supported by a National Institutes of Health multimillion dollar grant and works in collaboration with the Mary Lyon Centre in Harwell in the U.K., generates mouse strains each lacking a specific gene that has been knocked out or deleted. We also establish the primary characteristics of the knocked out mice as a way to understand how genes work and what functions they are responsible for,” said Dickinson, who also holds the Kyle and Josephine Morrow Endowed Chair at Baylor.

In her lab, Samuel and her colleagues took the work of the Knockout Mouse Project a step further by looking at the role the deleted genes played specifically in the retina. For this, the researchers developed the INSiGHT platform, which stands for the Identification of Neural and Synaptic integrity Genes by High Throughput screening. The system analyzes the expression of the candidate gene and the effect of its deletion on vascular patterning, cellular organization and synaptic arrangement in tissue samples.

The researchers received tissue samples from more than 100 different lines of knockout mice representing about 450 different animals and applied INSiGHT to determine which of those lines may be affected in several features of retina organization. They found 16 unique retinal regulatory genes. Fifteen of them had not been implicated before in aspects of neural development, wiring and vascular patterns that nurture the retina. Importantly, all of these genes have equivalent human genes and nine of them have been previously implicated in human neural disease.

“Of the 16 genes we uncovered, a few caught our attention,” Samuel said. “For instance, animals lacking the gene Slc44a1 show quite dramatic changes in the vasculature patterning in the retina. We are interested in studying this gene further because proper development and maintenance of retinal vascular networks are critical for normal visual function, both in mice and people.”

“This study is particularly exciting because in addition to helping understand the mechanisms underlying eye disease, it will likely provide insights into other neurological or cardiovascular disorders,” Dickinson said. “The eye is really like a little brain but with a built-in window to directly observe the biology. By combining imaging with large scale genetics and cell biological methods, we are beginning to understand gene roles that have not previously been described.”

Now that Samuel and her colleagues have INSiGHT worked out, they plan to expand their screen to look for more genes as well as determine how the genes they have already uncovered function in the retina and the brain.

“Our objective is to contribute to a key goal in the field, which is to map the compendium of genes that regulate the nervous system,” Samuel said.


Explore further:
Researchers reverse congenital blindness in mice

More information:
Cell Reports (2018). DOI: 10.1016/j.celrep.2018.07.090

Journal reference:
Cell Reports

Provided by:
Baylor College of Medicine

Tagged with:

About author

Related Articles