Breaking News
January 21, 2019 - Plan Your Plate | NIH News in Health
January 21, 2019 - Fecal occult blood test may improve CRC outcomes in some
January 21, 2019 - Mount Sinai joins with Paradigm and ReqMed to repurpose drug for treatment of MPS
January 21, 2019 - FDA Advisory Committee Votes on Zynquista (sotagliflozin) as Treatment for Adults with Type 1 Diabetes
January 21, 2019 - The causes and complications of snoring
January 21, 2019 - Placenta adapts and compensates when pregnant mothers have poor diets or low oxygen
January 21, 2019 - New implant could restore the transmission of electrical signals in injured central nervous system
January 21, 2019 - Rapid-acting fentanyl test strips found to be effective at reducing overdose risk
January 21, 2019 - Coronary Artery Calcium May Help Predict CVD in South Asians
January 21, 2019 - The mystery of the super-ager
January 21, 2019 - Scientists develop smart microrobots that can change shape depending on their surroundings
January 21, 2019 - Keep Moving to Keep Brain Sharp in Old Age
January 21, 2019 - Despite progress, gay fathers and their children still structurally stigmatized
January 21, 2019 - New drug for treating liver parasites in vivax malaria
January 21, 2019 - Merck recognized with 2018 Life Science Industry Award for best use of social media
January 21, 2019 - Coeur Wallis equips the canton of Valais with 260 SCHILLER defibrillators
January 21, 2019 - Scientists propose quick and pain-free method for diagnosing kidney cancer
January 21, 2019 - Signs of memory loss could point to hearing issues
January 21, 2019 - HeartFlow Analysis shows highest diagnostic performance for detecting coronary artery disease
January 21, 2019 - How Much Caffeine is Too Much?
January 21, 2019 - Take a timeout before you force your child to apologize
January 21, 2019 - Scientists design two AI algorithms to improve early detection of cognitive impairment
January 21, 2019 - Novel therapy for children with chronic hormone deficiency provides lifeline for parents
January 21, 2019 - Bioethicists call for oversight of poorly regulated, consumer-grade neurotechnology products
January 21, 2019 - Study shows hereditary hemochromatosis behind many cancers and joint diseases
January 21, 2019 - Short bouts of stairclimbing throughout the day can improve cardiovascular health
January 20, 2019 - Liver Transplant Survival May Improve With Race Matching
January 20, 2019 - Study implicates hyperactive immune system in aging brain disorders
January 20, 2019 - Cancer Diagnosis May Quadruple Suicide Risk
January 20, 2019 - Parkinson’s disease experts devise a roadmap
January 20, 2019 - Research brings new hope to treating degenerative brain diseases
January 20, 2019 - Scientists pinpoint a set of molecules that wire the body weight center of the brain
January 20, 2019 - Researchers get close to developing elusive blood test for Alzheimer’s disease
January 20, 2019 - UCLA researchers demonstrate new technique to develop cancer-fighting T cells
January 20, 2019 - Researchers discover how cancer cells avoid genetic meltdown
January 20, 2019 - Exercise makes even the ‘still overweight’ healthier: study
January 20, 2019 - University of Utah to establish first-of-its-kind dark sky studies minor in the US
January 20, 2019 - School-based nutritional programs reduce student obesity
January 20, 2019 - Improved maternity care practices in the southern U.S. reduce racial inequities in breastfeeding
January 20, 2019 - New enzyme biomarker test indicates diseases and bacterial contamination
January 20, 2019 - Republican and Democratic governors have different visions to transform health care, say researchers
January 20, 2019 - Researchers discover that spin flips happen in only half a picosecond in the course of a chemical reaction
January 20, 2019 - Suicide Risk Up More Than Fourfold for Cancer Patients
January 20, 2019 - Doctors find 122 nails in Ethiopian’s stomach
January 20, 2019 - UV disinfection technology eliminates up to 97.7% of pathogens in operating rooms
January 20, 2019 - Researchers discover mechanism which drives leukemia cell growth
January 20, 2019 - AHA: Infection as a Baby Led to Heart Valve Surgery for Teen
January 20, 2019 - Injection improves vision in a form of childhood blindness
January 20, 2019 - Multiple sclerosis therapies delay progression of disability
January 20, 2019 - New study finds infrequent helmet use among bike share riders
January 20, 2019 - Clearing up information about corneal dystrophies
January 20, 2019 - Researchers describe new behavior in energy metabolism that refutes existing evidence
January 20, 2019 - New study takes first step toward treating endometriosis
January 20, 2019 - Researchers find how GREB1 gene promotes resistance to prostate cancer treatments
January 20, 2019 - Replacing Sitting Time With Activity Lowers Mortality Risk
January 20, 2019 - A simple, inexpensive intervention makes birth safer for moms and babies in parts of Africa
January 19, 2019 - New anti-inflammatory compound acts as ‘surge protector’ to reduce cancer growth
January 19, 2019 - Significant flaws found in recently released forensic software
January 19, 2019 - New Leash on Life? Staying Slim Keeps Pooches Happy, Healthy
January 19, 2019 - Men and women remember pain differently
January 19, 2019 - Rising air pollution linked with increased ER visits for breathing problems
January 19, 2019 - Study uses local data to model food consumption patterns among Seattle residents
January 19, 2019 - The brain’s cerebellum plays role in controlling reward and social behaviors, study shows
January 19, 2019 - Relationship between nurse work environment and patient safety
January 19, 2019 - Pioneering surgery restores movement to children paralyzed by acute flaccid myelitis
January 19, 2019 - Genetic variants linked with risk tolerance and risky behaviors
January 19, 2019 - New research provides better understanding of our early human ancestors
January 19, 2019 - First-ever tailored reporting guidance to improve patient care and outcomes
January 19, 2019 - 4.6 percent of Massachusetts residents have opioid use disorder
January 19, 2019 - New study suggests vital exhaustion as risk factor for dementia
January 19, 2019 - New antibiotic discovery heralds breakthrough in the fight against drug-resistant bacteria
January 19, 2019 - Ural Federal University scientists synthesize a group of multi-purpose fluorophores
January 19, 2019 - Researchers identify new therapeutic target in the fight against chronic liver diseases
January 19, 2019 - Preparation, characterization of Soyasapogenol B loaded onto functionalized MWCNTs
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
Gene regulator associated with protein pileup in exfoliation glaucoma

Gene regulator associated with protein pileup in exfoliation glaucoma

image_pdfDownload PDFimage_print

In exfoliation glaucoma, a protein dandruff clogs the outflow pathway for the fluid in our eyes.

Scientists have evidence that variants of the same gene that enables us to make connective tissue by crosslinking proteins is associated with this unusual glaucoma.

Now they are looking in human eye tissue at a long piece of RNA that helps control expression of that LOXL1 gene with the idea that it may be a culprit in the destructive pileup of LOXL1 protein inside the eye.

A new, $440,000 grant from the National Eye Institute is helping Dr. Yutao Liu and his colleagues further explore the relationship between the gene and this long, noncoding RNA dubbed lncLOXL1.

A long-term goal is finding better treatment targets for this glaucoma, which is generally more aggressive and difficult to treat than its more common counterpart, primary open angle glaucoma, says Liu, vision scientist and human geneticist in the Department of Cellular Biology and Anatomy at the Medical College of Georgia at Augusta University.

“Variants of this gene are associated with the disease in every population we have studied worldwide,” Liu says, including Caucasians, blacks in South Africa, the Japanese as well as Southeast Asians in India. They found the expression of LOXL1 consistently elevated early in the disease in every population. Variants are basically a slight difference in the most usual sequence of letters in the DNA.

High levels of LOXL1 protein that clog outflow tracts for the eye’s aqueous humor also are a constant in all those patients. Still, there is conflicting laboratory evidence about the role of the suspect gene because neither removing or overexpressing it always results in the classic protein accumulation and high pressure inside the eye, at least in lab animals. So Liu and his team are also now looking at lncLOXL1, which regulates the gene’s expression.

So far they have seen the expression level of the gene and lncLOXL1 correlate in both gene variations the scientists have seen in the human populations they have studied. They also have seen that as disease progresses, the gene expression goes down even as the protein piles up, typically at about age 60.

One of the many things they want to know now is what happens to the lncLOXL1 expression in disease. Does its expression also go down when disease becomes symptomatic, or does its parallel expression with the gene part ways at that point?

Knowing that will help determine whether it might one day need to be turned up or down to help patients, Liu says.

They also are further refining exactly what lncLOXL1 does and how it does it by looking at what genes/proteins are affected when it’s knocked out and overexpressed.

“We are looking at what happens to expression of both the LOXL1 gene and its protein when we remove lncLOXL1 from the equation and when we overexpress it,” Liu says.

They are also looking at other factors floating in the eye fluid with disease. Along with way too much protein, there are proinflammatory factors like transforming growth factor beta one, a protein with a wide range of functions from helping cells mature, grow, differentiate and even die, to promoting an inflammatory response; cytokines secreted by immune cells; and hydrogen peroxide, a product of high levels of oxidative stress.

They want to know if lncLOXL1 needs one or all these factors to do the damage they think it does. If they block these factors, for example, does the destruction still happen? Liu has already seen that treatment of human eye cells with transforming growth factor beta one impacts expression of this long, noncoding RNA. Now he is looking at things like what happens to levels of the LOXL1 protein.

They also are looking at the impact of environmental factors like ultraviolet light, since proximity to sunlight, like individuals who live in the mountains of Iceland, is an established risk factor for exfoliation glaucoma.

“From what we have seen so far, we don’t think coding changes of this gene have anything to do with the disease, so it must be gene regulation,” Liu says, and that could mean lncLOXL1.

A handful of years ago, Liu and colleagues at Duke University did a genetic association study – which looked at genetic risk factors – and found that variants of the gene LOXL1 in the noncoding region were associated with exfoliation glaucoma. The variance was in a sequence of the gene’s DNA called the intron, which helps regulate gene expression, so how much of which proteins get made by the gene rather than actual protein production. Coding regions of genes that make proteins are called exons, and introns are considered non-coding regions.

The genetic variants appeared to impact not which proteins got made, but how much got made. With exfoliation glaucoma, it’s definitely too much.

In addition to clogging fluid paths, over time the protein pileup appears to nibble away at the endothelial cells that line blood vessels as well as the pericytes, contractile cells that wrap around the endothelial cells and help give blood vessel walls strength and flexibility. The protein also weakens zonules, transparent tendons that help hold the lens of the eye in place.

Although inflammation contributes to the destruction in exfoliation glaucoma, the immune system often does not eliminate the dandruff-like flakes congesting fluid flow of the eye. Pressure inside the eye soars and the eyedrops that help the more common open-angle glaucoma by increasing outflow and/or decreasing fluid production don’t work. Surgery to improve outflow often does not work long either.

The current studies are primarily using eye tissue from the lens capsule of 20 patients with exfoliation glaucoma as well as 20 patients who needed cataract surgery and are considered the controls. One thing both populations have in common is they are older, which is when cataracts and symptoms of exfoliation glaucoma both tend to surface.

Liu notes that not everyone with one of the known gene variants develops exfoliation glaucoma, and that as with many diseases, it’s likely a combination of genes and environment that’s causative.

The aqueous humor directly provides nutrition to the eye and the invaluable fluid is normally replaced about every 90 minutes.

In recent years, long, noncoding RNAs, which as the name implies are longer than some of their colleagues like microRNA, have been associated with an increasing number of diseases including a wide variety of cancers and cardiovascular disease.

Source:

https://www.augusta.edu/mcg/

Tagged with:

About author

Related Articles