Breaking News
October 23, 2018 - Researchers identify immune culprits linked to inflammation and bone loss in gum disease
October 23, 2018 - Despite lower risk factors, black men have higher rates of recidivism
October 23, 2018 - Study finds why pregnant women in mainland China, Hong Kong and Taiwan prefer cesarean delivery
October 23, 2018 - AbbVie’s U-ACHIEVE Phase 2b/3 dose-ranging study improves outcomes in patients with ulcerative colitis
October 23, 2018 - NCI grant awarded to Abramson Cancer Center to study CAR T cells In solid tumors
October 23, 2018 - Scientists use electron microscope to study chemical transformation in catalytic cross-coupling reaction
October 23, 2018 - Research offers new hope to men who received childhood cancer treatment
October 23, 2018 - Adverse Childhood Experiences Tied to Burnout in BSN Students
October 23, 2018 - High levels of oral disease among elite athletes affecting performance
October 23, 2018 - Study examines effect of immediate vs delayed pushing during labor on delivery outcomes
October 23, 2018 - LU-RRTC to spearhead capacity-building efforts for racial and ethnic populations
October 23, 2018 - Maintenance therapy with olaparib improves progression-free survival in advanced ovarian cancer patients
October 23, 2018 - Organic food may protect against cancers finds study
October 23, 2018 - Interweaving anxiety disorder associated with stuttering remains unrecognized
October 23, 2018 - Cannabis oil shown to significantly improve Crohn’s disease symptoms
October 23, 2018 - Knowledge of sex differences in lower urinary tract may help stimulate breakthroughs in diagnosis, management
October 23, 2018 - Common antibodies associated with myocardial infarction
October 23, 2018 - Study reveals new treatment option for women with advanced breast cancer resistant to hormone therapy
October 23, 2018 - Brain’s ‘Self-Control’ Center May Be Key to Weight-Loss Success
October 23, 2018 - Prosthetic valve mismatches common in transcatheter valve replacement, ups risk of death
October 23, 2018 - Can virtual reality help people become more compassionate?
October 23, 2018 - Screen time eclipsed outdoor time for most students, shows study
October 23, 2018 - SLU researcher seeks to find solutions for ‘chemo brain’ symptoms and side effects of opioids
October 23, 2018 - Plastics now commonly found in human stools
October 23, 2018 - Zoledronic acid increases disease-free survival in premenopausal women with HR+ early breast cancer
October 23, 2018 - Cancer survivors at risk for heart failure during, after pregnancy
October 23, 2018 - Stanford project brings health education videos to mothers in South Africa
October 23, 2018 - HIV-infected Hispanics at higher risk of developing HPV-related cancers, finds study
October 23, 2018 - Politicians hop aboard ‘Medicare-for-all’ train, destination unknown
October 23, 2018 - Study suggests rising childhood obesity rates as cause for serious hip disease in adolescents
October 23, 2018 - Study highlights existence of barriers to early clinical trial access for adolescents and young adults
October 23, 2018 - Protein sequencing technique could revolutionize biomedical research
October 23, 2018 - Canon Medical to showcase world’s first Ultra-High Resolution CT system at ASTRO 2018
October 23, 2018 - Spectrum Pharmaceuticals Announces Release of Updated Poziotinib Data From MD Anderson Phase 2 Study in Non-Small Cell Lung Cancer Patients
October 23, 2018 - Cancer stem cells use ‘normal’ genes in abnormal ways
October 23, 2018 - Bad Blood: A conversation with investigative reporter John Carreyrou | News Center
October 23, 2018 - As U.S. fertility rates collapse, finger-pointing and blame follow
October 23, 2018 - Researchers develop promising targeted strategy to treat chemo-resistant blood cancer
October 23, 2018 - Pilot clinical trial shows effectiveness of bioelectronic medicine device for lupus
October 23, 2018 - Genentech’s combination therapy improves outcome in patients with non-squamous non-small cell lung cancer
October 23, 2018 - 11th World Stroke Congress examines high stroke impact in low- and middle-income countries
October 22, 2018 - Breast cancer survival could be extended with two new drug combinations
October 22, 2018 - Researchers discover how acne-causing bacteria resist treatment
October 22, 2018 - Cancer trial shows treating the prostate with radiotherapy improves survival
October 22, 2018 - New hope for a drug to treat lymphedema symptoms
October 22, 2018 - Immune-Based Treatment Helps Fight Aggressive Breast Cancer, Study Finds
October 22, 2018 - Takeda announces positive Phase 3 ALTA-1L data in first-line therapy for advanced ALK+ NSCLC
October 22, 2018 - Paternal exercise has significant impact on child’s lifelong metabolic health
October 22, 2018 - Targeting specific genomic mutation in breast cancer improves survival
October 22, 2018 - Loss of tumor protein p53 helps cancer cells grow in hostile environment
October 22, 2018 - IDT to demonstrate CRISPR expertise at European-focused events
October 22, 2018 - Breathing through the nose improves memory consolidation
October 22, 2018 - Recreational Marijuana Now Legal in Canada
October 22, 2018 - Scientists reveal drumming helps schoolchildren diagnosed with autism
October 22, 2018 - A stage IV cancer patient discusses what it means to live well with serious illness
October 22, 2018 - In Kids with Autism, Short Questionnaire May Detect GI Disorders
October 22, 2018 - Innovative strategy opens up new avenue of treatment for anthrax infections
October 22, 2018 - Merck presents MK-1454 Phase 1 data for treatment of advanced solid tumors or lymphomas
October 22, 2018 - Aspirin may be effective in preventing blood clots after knee replacement
October 22, 2018 - Drug cocktail that increases lifespan discovered
October 22, 2018 - Gilead Sciences presents Phase 3 results of filgotinib in biologic-experienced rheumatoid arthritis at 2018 ACR/ARHP Annual Meeting
October 22, 2018 - Study shows potential positive impact of group prenatal care on birth outcomes
October 22, 2018 - Immunotherapy with pembrolizumab extends survival in metastatic or recurrent head and neck cancer
October 22, 2018 - Health Tip: Keep Ticks Away
October 22, 2018 - Obsessive-compulsive disorder – Genetics Home Reference
October 22, 2018 - Researchers find disrupted functional connectivity in cerebellum of adults with HF-ASD
October 22, 2018 - Deciphera presents Phase 1 clinical results of DCC-2618 in patients with gastrointestinal stromal tumors
October 22, 2018 - Combination of Opdivo and Yervoy shows four-year survival benefits in patients with advanced melanoma
October 22, 2018 - Overcoming bottlenecks in early drug discovery with the power of sound
October 22, 2018 - Scientists discover genes that contribute to ADHD development
October 22, 2018 - Incyte announces Phase 2 FIGHT-202 trial data in patients with cholangiocarcinoma
October 22, 2018 - FDA approves update to Rituxan label to include information on treatment of rare forms of vasculitis
October 22, 2018 - At-home biofeedback therapy effective in relieving difficult-to-treat constipation
October 22, 2018 - Merck presents KEYNOTE-057 trial results for patients with high-risk non-muscle invasive bladder cancer
October 22, 2018 - People with periodontal disease less likely to reach healthy blood pressure ranges
October 22, 2018 - Phase III LONSURF study shows progression-free survival in patients with refractory metastatic gastric cancer
October 22, 2018 - Primary care doctors ‘not doing enough’ to curb STDs
October 22, 2018 - Pfizer announces PALOMA-3 trial results in patients with HR+, HER2- metastatic breast cancer
October 22, 2018 - ImmunoGen announces study results of platinum-resistant ovarian cancer therapy at ESMO 2018 Congress
October 22, 2018 - Study findings could set new standard of care for advanced anal cancer
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