Breaking News
November 13, 2018 - FDA Approves Keytruda (pembrolizumab) in Combination with Carboplatin and Either Paclitaxel or Nab-Paclitaxel for the First-Line Treatment of Patients with Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)
November 13, 2018 - Scientists take big step toward finding non-addictive painkiller
November 13, 2018 - Diabetes medication reduces risk of heart failure hospitalization
November 13, 2018 - Achieving high follow-up rates for violently injured patient population is feasible
November 13, 2018 - Shortage of specific gene ‘silencing’ molecules linked with pediatric low-grade gliomas
November 13, 2018 - Abx-Resistant Enterobacteriaceae Tied to Clinical Failure in UTI
November 13, 2018 - US approves first new type of flu drug in 2 decades
November 13, 2018 - Is zinc the link to how we think? Some evidence, and a word of warning
November 13, 2018 - Dispelling taboos, Michelle Obama talks IVF and miscarriage
November 13, 2018 - Medical experts discuss future challenges of healthcare at HSMA’s inaugural conference
November 13, 2018 - Growth and spread of deadly eye tumor suppressed in cells, animals
November 12, 2018 - Study finds huge shortfall in use of home-based medical care by frail seniors
November 12, 2018 - Cocaine Cut With Anti-Worming Drug, Levamisole, May Cause Brain Damage
November 12, 2018 - Obese mice lose a third of their fat using a natural protein
November 12, 2018 - Behind many a Parkinson’s case lurks a mutation in a gene called LRRK2 — why?
November 12, 2018 - Drug with fish oil cuts risk of heart attack, stroke, study finds
November 12, 2018 - Mild exposure to single blast can induce meaningful pathogenic effects, study shows
November 12, 2018 - Miniature pacemakers aim to make heart procedures for infants less invasive, more efficient
November 12, 2018 - Treating pre-cancerous stem cells at early stage could be key to preventing bowel cancer
November 12, 2018 - Kawasaki disease triggered by a combination of factors
November 12, 2018 - Optibrium and University of Nottingham Collaborate on Innovative Teaching Programme
November 12, 2018 - RNA defects linked to multiple myeloma progression in high risk patients
November 12, 2018 - Science is on trial – and we need doctors to provide the defense
November 12, 2018 - Salk researchers receive $19.2 million to unravel mysteries of age-related cognitive decline
November 12, 2018 - KE Eye Centers offer new solution for patients with myopia and astigmatism
November 12, 2018 - Trumpeted new Medicare Advantage benefits will be hard for seniors to find
November 12, 2018 - Biogen and Eisai Announce Presentation of Detailed Analyses from the Phase 1b Long-Term Extension Study of Aducanumab at Clinical Trials on Alzheimer’s Disease (CTAD)
November 12, 2018 - Scientists reveal new cystic fibrosis treatments work best in inflamed airways
November 12, 2018 - Hands-Only CPR training kiosks can teach life-saving skills in just minutes
November 12, 2018 - Inexpensive and effective drug does not reduce major adverse cardiovascular event rates
November 12, 2018 - Testing coronary calcium levels can better predict patient’s risk for coronary heart disease
November 12, 2018 - FDA conducts mass seizure of food and medical products held under insanitary conditions
November 12, 2018 - FDA Approves Invokana (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease
November 12, 2018 - Hormone helps reverse brain damage caused by obesity
November 12, 2018 - Grants aim to provide better cancer clinical trial access for military veterans
November 12, 2018 - Mitochondrial DNA may have strong influence on cellular metabolism and disease susceptibility
November 12, 2018 - High stakes, entrenched interests and the Trump rollback of environmental regs
November 12, 2018 - Stem cells transplanted for treatment of Parkinson’s disease
November 12, 2018 - Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Losartan Potassium and Hydrochlorothiazide Due to the Detection of Trace Amounts of NDEA (N-Nitrosodiethylamine) Impurity Found in the Active Pharmaceutical Ingredient (API)
November 12, 2018 - Protein found in patients with severe asthma can help identify who would benefit from targeted drugs
November 12, 2018 - Experts develop a list of competencies in antimicrobial prescribing and stewardship
November 12, 2018 - Allied BioScience receives approved label from EPA for new bacteriostatic surface coating
November 12, 2018 - MR Solutions displays elegant bench top CT scanner with clip-on PET and SPECT at EANM congress
November 12, 2018 - FDA announces emergency use authorization of Ebola fingerstick test with portable reader
November 12, 2018 - Grieving spouses with sleep problems have increased risk of chronic immune activation
November 12, 2018 - Exercise routines affect mental health in Japanese expatriates
November 12, 2018 - Fish oil and vitamin D pills no guard against cancer or serious heart trouble
November 12, 2018 - Excess Gestational Weight Gain Not Better for Child Bone Health
November 12, 2018 - Immune receptor provides protective immunity against Group A Streptococcus
November 12, 2018 - Scientists develop new method to produce irradiated nanomaterials for medical applications
November 12, 2018 - Blue light exposure decreases blood pressure
November 12, 2018 - Researchers discover two proteins essential for development of skeletal muscle
November 12, 2018 - Yelp reviews help understand strengths, weaknesses of emergency departments and urgent care centers
November 12, 2018 - Adolescent obesity linked with increased risk of pancreatic cancer later in life
November 12, 2018 - AHA: Poor Teeth-Brushing Habits Tied to Higher Heart Risk
November 12, 2018 - Researchers find how natural killer cells regulate protective HIV antibodies
November 12, 2018 - Rutgers receives $4.2 million federal grant to improve mental health services
November 12, 2018 - Sussex scientists develop a piece of hardware to show how brains function
November 12, 2018 - Study shows pivotal role of parents in efforts to change sexual orientation of LGBT teens
November 12, 2018 - Neck scan detects dementia way before symptoms appear
November 12, 2018 - Risk-profiling can benefit HIV prevention
November 12, 2018 - New thrombolytic based on magnetite nanoparticles successfully tested on animals
November 12, 2018 - Smoking rates go down in the US, lowest since 1965
November 12, 2018 - Phase III Trial of Darolutamide in Patients with Non-metastatic Castration-resistant Prostate Cancer Meets Primary Endpoint
November 12, 2018 - Moderate exercise before conception resulted in lower body weight, increased insulin sensitivity of offspring
November 11, 2018 - Community choirs for older adults reduce loneliness and increase interest in life
November 11, 2018 - Trevena Receives Complete Response Letter for Oliceridine from FDA
November 11, 2018 - More adults and children are using yoga and meditation
November 11, 2018 - Female smokers at greater risk of heart attacks, finds study
November 11, 2018 - Happy Childhood Memories Associated With Better Health
November 11, 2018 - X-linked infantile spinal muscular atrophy – Genetics Home Reference
November 11, 2018 - RNA thought to spread cancer shows ability to suppress breast cancer metastasis
November 11, 2018 - Study finds that thymus plays key role during normal pregnancy
November 11, 2018 - Exploring why some athletes ice their muscles after exercise
November 11, 2018 - Female Genital Mutilation Decreasing in African Nations
November 11, 2018 - Are humans immune to the CRISPR-Cas9 gene editing scissors?
November 11, 2018 - Breastmilk and saliva mixtures regulate oral microbiome of newborn babies
November 11, 2018 - Learning familiar faces through social interactions reduces variability in face recognition
November 11, 2018 - New open source decision support tool could help clinicians chose chemotherapy drugs
November 11, 2018 - New weapons drawn in global TB fight
Immune cells in the retina can spontaneously regenerate

Immune cells in the retina can spontaneously regenerate

image_pdfDownload PDFimage_print
Microglia in a healthy adult mouse retina. Credit: Wai T. Wong, National Eye Institute

Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish their normal organization and function. The findings point to potential therapies for controlling inflammation and slowing progression of rare retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the most common cause of blindness among Americans 50 and older. A report on the study was published online today in Science Advances.

“Neuroinflammation is an important driver of the death of neurons in retinal diseases,” said Wai T. Wong, M.D., Ph.D., chief of the NEI Section on Neuron-Glia Interactions in Retinal Disease, and the study’s lead investigator. “Our study is foundational for understanding ways to control the immune system in the retina.” Control of the immune system is important for developing new treatments for a variety of eye conditions, including AMD, RP, or for certain types of retinal injury.

The retina is a thin layer of cells in the back of the eye that includes light-sensing photoreceptor cells and other neurons involved in transmitting visual information to the brain. Mixed in with these cells are microglia, specialized immune cells that help maintain the health of the retina and the function of retinal neurons. Microglia are also present in other parts of the central nervous system, including the brain. In a healthy retina, communication between neurons and microglia is important for maintaining the neuron’s ability to send signals to the brain. When the retina is injured, however, microglia have an additional role: They migrate quickly to the injury site to remove unhealthy or dying cells. However, they can also remove healthy cells, contributing to vision loss. Studies show that in degenerative retinal disorders like AMD and RP, inhibiting or removing microglia can help retain photoreceptors, and thus slow vision loss. But return of microglia is still important to support the retina’s neurons.

Wong and colleagues were interested in understanding what happens in the retina after microglia have been eliminated, particularly whether the cells could return to their normal arrangement and fulfill their normal functions. To test this, they depleted the microglia in the retinas of mice using the drug PLX5622 (Plexxikon), which blocks the microglial CSF-1 receptor. Microglia depend on continuous signals through this receptor for survival. Interruption of this signaling for several days caused the microglia to nearly disappear, leaving just a few cells clustered around the optic nerve—the cable-like bundle of nerve fibers that carries signals from the retina to the brain—in the mouse retinas. Since loss of microglia for a short time doesn’t affect the function of neurons, removing microglia temporarily—in order to reduce inflammation for example—could potentially be useful as a therapeutic intervention for degenerative or inflammatory disorders of the retina.

“If we were to get rid of the microglia while a large, inappropriate immune response was happening,” said Wong, “we might be able to miss the worst of the inflammation, but still come back into balance at a later point in time. We could hit pause on the immune system in the retina in a directed way.”

Within 30 days after stopping the drug, Wong and colleagues found that the microglia had repopulated the retina, returning to normal density after 150 days. Using a novel method for visually tracking microglial movements in the retina, they determined that the returning microglia initially grew in clusters near where the optic nerve leaves the eye. Gradually, new microglia expanded outwards towards the edges of the retina. Over time, the cells re-established an even distribution across and through the various layers of the retina.

Images of mouse retina after being treated with a drug that nearly eliminates immune cells called microglia. On day 0 when the drug was stopped, nearly all microglia are gone, except for a few near the optic nerve head (center dark spot). Seven days later, microglia have migrated across the retina, and by day 10 they have increased in number. Credit: Wai T. Wong, National Eye Institute

“The organization of these immune cells is quite elaborate, and all the organization comes right back,” Wong said. “We can actually image the eye and watch these cells divide and split and migrate as part of the repopulation response.”

To test whether the new microglia were fully functional, the researchers used an injury model where photoreceptor cells are damaged by bright light. The new microglia were able to activate and migrate to the injury site normally. In addition, using electroretinography (ERG), a technique that measures the electrical signals generated by retinal neurons after being stimulated with light, the researchers tested the health of different groups of neurons. They found that the microglia were able to communicate with and fully maintain the function of neurons in the retina, especially when the depletion was short-lived.

Drugs that remove microglia are now administered systemically, affecting the brain and other parts of the central nervous system. More research is needed to find ways to administer these drugs directly to the retina, sparing off-target tissues.

AMD is the leading cause of vision loss among older Americans. It causes damage to the central part of the retina, the light-sensitive tissue at the back of the eye. AMD often has very few symptoms in its early stages; but in later stages, it causes loss of the central, straight-ahead vision needed for activities like reading and driving.

RP is an inherited disorder that results in progressive death of photoreceptors and subsequent vision loss. People with RP slowly develop tunnel vision. They may have difficulty performing essential tasks of daily living such as reading, driving, walking without assistance, or recognizing faces and objects.


Explore further:
Chinese scientists decipher origins of repopulated microglia in brain and retina

More information:
“Repopulating microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation” Science Advances (2018). advances.sciencemag.org/content/4/3/eaap8492

Journal reference:
Science Advances

Provided by:
National Eye Institute

Tagged with:

About author

Related Articles