King-Wai Yau, Johns Hopkins University, showed in mammalian retinal cells that one special type of light-sensing photoreceptors uses two different pathways at the same time to transmit electrical signals to the brain. The work also reveals that such photoreceptors, according to the researchers, may have ancient origins. To read this Hopkins news story. (CLICK HERE).

Nazlee Zebardast, Mass Eye and Ear, and collaborators combined retinal imaging, genetics, and big data to estimate how likely a person is to develop eye and systemic diseases. They found significant associations between thinning of retinal layers and risk of developing ocular, cardiac, pulmonary, metabolic, and neuropsychiatric diseases. To read this MEEI news story, (CLICK HERE).

Shukti Chakravarti, New York University Langone Health, and collaborators developed the models, called organoids, to study gene expression of the eye’s outermost surface during development. “Our study is the first to examine human corneal organoids at a single-cell resolution,” she said. “With their 3D structures and coexisting cell types they allow the study of cellular signaling and cell–cell interactions in a more natural environment.” To read this NYU Lagone Health story, (CLICK HERE).

Louis Pasquale, Mount Sinai Health System, and collaborators Oana Zeleznik and Jae Kang, Harvard University, discovered that lipid metabolism is dysregulated in and associated with primary open-angle glaucoma, the most common type of glaucoma. Based on data from thousands of study participants, the researchers found that higher levels of two lipids—diglycerides and triglycerides —were associated with an increased risk of glaucoma. The findings raise questions about whether statin use could lower the risk of glaucoma. To read this Mt. Sinai news story. (CLICK HERE).

Douglas Jabs, Johns Hopkins University; Nisha Acharya, University of California San Francisco; and collaborators in the NEI-funded MUST Research Group compared three treatments for persistent macular edema in patients with uveitis. Uveitis is a group of inflammatory conditions that affect the internal tissues of the eye. Macular edema is build-up of fluid in the eye’s retina. Compared with methotrexate or ranibizumab, corticosteroid treatment achieved greater reductions in edema and was the only therapy that improved vision. To read this NEI news story, (CLICK HERE).

Claude Desplan, Isabel Holguera, Nikolaos Konstantinides, and Anthony Rossi, New York University, also revealed factors regulating neuron development from a study of the visual system of fruit flies, uncovering similarities with human brain development. To read this New York University news article (CLICK HERE).

Xin Li and Sihai Dave Zhao, University of Illinois, uncovered molecular players that help control timing of nervous system cell differentiation. The nervous system is made up of diverse cells that arise from cell progenitors in a specific time-dependent pattern. The team used the fruit fly (drosophila) as a model to study the temporal patterning of neural progenitors, called neuroblasts. To read this University of Illinois news article (CLICK HERE).

Clayton Curtis and Yuna Kwak, New York University, published research that helps explain how working memory is “formatted”—a finding that enhances our understanding of how visual memories are stored. Using experimental and analytical techniques, they revealed the format of working memory representations in the brain. To read this New York University news article (CLICK HERE).

Krzysztof Palczewski, University of California Irvine, reported data from a mouse study that suggests base editing could be used in humans to protect vision from inherited retinal diseases such as Leber congenital amaurosis. Base editing corrects point mutations—one-letter errors in DNA code. Such mutations cause thousands of mostly rare diseases. Palczewski stated “if scientists align behind this approach, there is a chance that in 10 years, all inherited retinal diseases could be treatable.” To read this University of California, Irvine news article (CLICK HERE).

NEI featured Konstantin Petrukhin, Columbia University, and his discovery of a promising drug candidate called LBS-008 for treating age-related macular degeneration (AMD). The story highlights the NIH Blueprint Neurotherapeutics Network, the trans-NIH consortium that gave Petrukhin access to industry-style drug development services and expertise. Creation of the network was NIH’s response to the relatively low number of potential therapies for neurodegenerative disorders that enter patient testing. Belite Bio, Inc., picked up LBS-008 and is currently testing the drug in a clinical trial for Stargardt disease. To read this NEI news article (CLICK HERE).

Allison Ludwig, David Gamm,  Shaoqin (Sarah) Gong, and Zhenqiang (Jack) Ma, University of Wisconsin, developed a micro-molded scaffolding photoreceptor “patch” designed to be implanted under a damaged or diseased retina. The team plans to continue optimizing its scaffolding shape, fabrication technique, and bio-resorbable materials for faster production to satisfy future surgical needs. In the meantime, the current iteration of the scaffolding patch is almost ready for surgical testing in large animals. If successful, the patch will eventually be tested in humans. To read this University of Wisconsin news article (CLICK HERE).

Michael Kass, Washington University in St. Louis, and colleagues from the NEI-funded Ocular Hypertension Treatment Study reported that not all patients with elevated eye pressure need pressure-lowering treatment to prevent vision loss from glaucoma. The findings were based on the analysis of 20-year follow-up data. According to Kass, pressure-lowering treatment can be delayed until early damage is detected without adversely affect long-term outcomes. To read this Washington University news story (CLICK HERE).

NEI’s functional imaging consortium, a part of the NEI Audacious Goals Initiative, is pioneering noninvasive technologies to monitor the function of the retina’s light-sensing neurons and their connections to the brain. NEI Science Writer Kathryn DeMott summarizes the consortium’s accomplishments and explains how the developing technologies may be used. To read this NEI news story (CLICK HERE).

Kevin Chan, NYU Langone, restored optic nerve signals between the brain and eye to near-normal levels in a rat model using citicoline, a major source of choline, a building block in the membranes that line nerve cells and enhance nerve cell communication. While Chan’s research confirmed that elevated eye pressure contributes to nerve damage in glaucoma, it also showed that citicoline reduces vision loss in rats without reducing fluid pressure in the eye. “Our study suggests that citicoline protects against glaucoma through a mechanism different from that of standard treatments that reduce fluid pressure,” he said. To read this NYU Langone news story (CLICK HERE).

Bruce Vogel and colleagues found insights into age-related macular degeneration (AMD) by studying round worms. Several years ago, genomic studies found a link between AMD and the immune protein complement factor H (CFH). But how CFH exerts its effect still isn’t fully understood. “Our findings suggest that complement factor H plays a role in maintaining the organization of photoreceptor cilia, and this process may be defective in AMD,” said Vogel. To read this University of Maryland news story (CLICK HERE).

“In patients who’ve lost their vision from advanced-stage retinal diseases, the artificial retina would mimic the function of photoreceptors…” said Nicole Wagner, chief executive officer of LambdaVision, an NEI small business grantee. LambdaVision is optimizing production of their artificial retina on the International Space Station, where microgravity provides conditions for constructing the multilayered protein-based artificial retina. To read this NEI news story (CLICK HERE).

Gustavo Aguirre and William Beltran, University of Pennsylvania, demonstrated that delivering a normal copy of either the canine or human version of the NPHP5 gene restores vision in dogs with NPHP5 mutations. Similar NPHP5 mutations occur in the human disease Leber congenital amaurosis, where the light-sensing cone photoreceptors fail to develop normally. “What’s amazing is that you can take this disease in which cone cells have incompletely formed, and the therapy restores their function—they had no function whatsoever before—and recover their structure,” said Aguirre. To read this University of Pennsylvania news story (CLICK HERE).

NEI Director Michael F. Chiang issued a statement calling for imaging device makers to standardize their data formatting, joining the American Academy of Ophthalmology and others who say such standardization will enable communication across health care providers, improve quality of care, and enhance the creation of datasets for research. “Not all health care providers speak the same language, but the software in their clinical imaging devices can and should,” Chiang said. To read this NEI statement (CLICK HERE).

Raj Maturi, Indiana University, and the DRCR Retina Network showed that early treatment with anti-VEGF injections slows diabetic retinopathy. However, two years into the four-year study its effect on vision was similar to standard treatment, which usually begins at the onset of late disease. “While it is possible that preventive injections of anti-VEGF drugs may help protect vision in the longer-term, we saw no effect on vision at two years,” said Maturi. To read this NEI news story (CLICK HERE).

Ruchira Singh, University of Rochester, and colleagues developed a living 3D model of the human retina. Their model combines stem cell-derived retinal tissue and vascular networks with bioengineered synthetic materials in a 3D matrix. The researchers are using the model system to investigate the underlying mechanisms of the wet form of age-related macular degeneration. To read this University of Rochester news story (CLICK HERE).

Martin Friedlander, Scripps Research Institute, and collaborators found more than a dozen PHGDH gene variants related to macular telangiectasia type 2 (MacTel), a retinal disease that causes loss of central vision. The PHGDH gene is key to making the amino acid serine. In people with MacTel, low serine levels lead to a build-up of lipids that are toxic to the retina’s light-sensing photoreceptors. To read this Scripps Research news story (CLICK HERE).

NIH-funded study shows early eye injections reduce vision-threatening complications; effect on vision similar to standard treatment. To read this NIH news story (CLICK HERE).

Duygu Kuzum, University of California San Diego, and colleagues developed a device that can run neural network computations using 100 to 1000 times less energy and area than current, state-of-the art CMOS-based hardware. Neural networks comprise connected layers of artificial neurons that can be applied to technology such as automated object recognition in self-driving cars. To read this UC San Diego news story (CLICK HERE).

The National Eye Institute (NEI) Data Commons now enables researchers to access data from patients with macular degeneration who participated in the Age-related Eye Disease Study 2 (AREDS2). The database complements newly available stem cell lines created by the New York Stem Cell Foundation Research Institute (NYSCF) from blood cells of AREDS2 study participants. Together, these resources will accelerate the discovery of therapies for age-related macular degeneration (AMD) and other blinding conditions. The NEI and the NYSCF will host a joint webinar on March 30 to introduce the new NEI AMD Integrative Biology Initiative data portal, housed within the NEI Data Commons.

Johnny Tam and colleagues in the NEI Clinical and Translational Imaging Unit noninvasively visualized light-sensing photoreceptors in greater detail than ever before. The researchers reported in Optica how they improved imaging resolution by a third by selectively blocking the light used to image the eye. To read this NEI news story (CLICK HERE).

Stephen Strittmatter, Yale School of Medicine, and researchers identified 40 genes actively involved in suppression of axon regeneration in central nervous system cells. By editing out one of those genes, they were able to restore axons in ocular nerves of mice damaged by glaucoma. “This opens a new chapter in regeneration research,” said Strittmatter. The research was funded through NEI’s Audacious Goals Initiative. To read this Yale news story (CLICK HERE).

Mary Elizabeth Hartnett, University of Utah, revealed in mouse experiments that an oxidized form of cholesterol called oxysterol 7-ketocholesterol (7KC) can lead to fibrosis (scarring) in the retina. The fibrosis observed by Hartnett is similar to what’s seen in cases of neovascular or ‘wet’ age-related macular degeneration (AMD) that respond poorly to anti-VEGF treatment. “Any time we give anti-VEGF to a patient there can be up to a 50% chance they will ultimately fail treatment…These findings provide a potential explanation for fibrosis and suggest that if we can interfere with this process, we might be able to improve outcomes in many more patients with neovascular AMD,” said Hartnett. To read this UT Health Moran Eye Center news story (CLICK HERE).

Hirofumi Morishita, Mount Sinai, and fellow researchers identified a neural pathway through which the brain detects errors and guides behavioral improvement. This process, called cognitive control, is frequently dysregulated in a range of psychiatric disorders. To read this Mount Sinai news story (CLICK HERE).

Joseph Arboleda-Velasquez and Leo Kim, Harvard, reported that Runt-related transcription factor 1 (RUNX1) inhibition presents a new therapeutic approach in AMD treatment. “RUNX1 inhibitors hold significant promise to complement or replace anti-VEGF therapies for patients in which anti-VEGF therapy is no longer effective, and with the potential to be administered topically it could be transformative in the field,” said Arboleda-Velasquez. To read this Elsevier news story (CLICK HERE).

Janey Wiggs, Harvard University, and an international team of researchers identified 44 new gene loci and confirmed 83 previously reported loci linked to glaucoma. Loci denote locations on a gene. “These new findings come out of the highest-powered genome-wide association study of glaucoma to date, and show the power of team science and using big data to answer questions when research groups around the world join forces,” said Wiggs. The findings will help identify new therapeutic targets. To read this Harvard news story (CLICK HERE).

A New Vision for AAV-Delivered Gene Therapies:
George Church and Constance Cepko, Harvard University, designed a strategy to help gene therapies avoid unwanted stimulation of the immune system. The adeno-associated virus (AAV) has been a leading vehicle for delivery of therapeutic genes because it is non-pathogenic and efficiently targets a variety of cells and tissue types. The researchers modified the AAV genome by adding sequences that inhibit TLR9, a cell receptor involved in inflammation. Importantly, the study highlights that non-TLR9 pathways likely contribute to inflammation in AAV injections in the eye’s gel-like vitreous. To read this Harvard news story (CLICK HERE).

Cold Sores: Gere’s How Stress, Illness and Even Sunburn Trigger Flareups:
Anna Cliffe, University of Virginia, shed light on the causes of herpes simplex virus (HSV) flare-ups. More than half of Americans are infected with HSV, which lurks inside neurons, waiting for the right moment to reactivate. Recurrent reactivation in the eye leads to herpes keratitis, which, if left untreated, can result in blindness. Cliffe and her collaborators developed an HSV mouse model and found that the virus highjacks an important immune response via the cytokine interleukin beta.  To read this University of Virginia news story (CLICK HERE).

New Research Sheds Light on Vision Loss in Batten Disease:
Ruchira Singh and colleagues at the University of Rochester discovered that normal CLN3 gene function is crucial for proper function of the retina’s pigmented epithelial cells (RPE). Vision loss is often the first symptom of Batten disease, a rare genetic disorder that also causes learning and behavior problems, slow cognitive decline, seizures, and loss of motor control in children. The researchers’ findings are based on studies of tissues that they re-engineered from Batten disease patients. Understanding how RPE cell dysfunction contributes to photoreceptor cell loss in Batten disease is an important first step, and it will enable researchers to target specific cell type in the eye using potential future gene therapies, cell transplantation, and drug-based interventions, said Singh. To read this University of Rochester news story (CLICK HERE).

Breakthrough by Moran Eye Center Scientist; Colleagues Fuels New Line of Disease Research:
Paul Bernstein at the University of Utah Moran Eye Center and colleagues invented a method for synthesizing large quantities of very-long-chain polyunsaturated fatty acids (VLC-PUFAs) to evaluate their potential sight-preserving properties. The study determined that VLC-PUFA supplementation increased levels of the lipids in the retina and also improved visual function in normal mice and in mice with a defect in the ELOVL4 enzyme, which is involved in the body’s production of VLC-PUFAs. To read this University of Utah news story (CLICK HERE).

HIV Drugs May Help Prevent Blinding Macular Deg­eneration:
Jayakrishna Ambati, University of Virginia, and colleagues identified a group of drugs that may help stop the dry form of age-related macular degeneration (AMD). The researchers reviewed four different health insurance databases and found that people taking nucleoside reverse transcriptase inhibitors were almost 40% less likely to develop the potentially blinding disease. The researchers think the drug acts by interrupting Alu—RNA fragments that Ambati previously implicated in AMD pathogenesis. “A clinical trial of these inflammasome-inhibiting drugs is now warranted,” he said. To read this University of Virginia Health news story (CLICK HERE).

A Rift in the Retina May Help Repair the Optic Nerve:
Thomas Johnson, Johns Hopkins University, and colleagues reported that in mice removing the retina’s internal limiting membrane—a structure that separates retinal neurons from the eye’s gel-like vitreous—facilitates the integration of transplanted retinal ganglion cells (RGCs). The RGCs have long axons that carry visual signals from the eye to the brain. Optic neuropathies such as glaucoma destroy RGCs. “The idea of restoring vision to someone who has lost it from optic nerve disease has been considered science fiction for decades. But in the last five years, stem cell biology has reached a point where it’s feasible,” he said. To read this Hopkins news story (CLICK HERE).

A Niche for the Eye:
Ting Xie, Stowers Institute, and colleagues found a signaling pathway that affects eye development and maintenance in the ciliary body—a tissue in the eye that controls lens shape and produces aqueous fluid. “The next important question is what other protein factors secreted by the ciliary body are important for maintaining the cornea, the lens, and the retina. Some of these factors could be involved directly in eye diseases,” said Xie. To read this Stowers news story (CLICK HERE).

AI Algorithms Detect Diabetic Eye Disease Inconsistently:
Aaron Lee, University of Washington School of Medicine, and colleagues found that artificial intelligence algorithms for detecting diabetic retinopathy don’t measure up to their claims. The team deployed 7 algorithm-based technologies on retinal images from nearly 24,000 veterans who sought diabetic retinopathy screening and found that only one matched human screeners. To read this University of Washington news story (CLICK HERE).

Routine Eye Scans May Give Clues to Cognitive Decline in Diabetes:
George King, Joslin Diabetes Center, showed that routine eye imaging can identify changes in the retina that may be associated with cognitive disorders in older people with type 1 diabetes. King’s team found strong associations between study participants’ performance on memory tasks and structural changes in deep retina blood vessel networks imaged by optical coherence tomography. To read this Joslin news story (CLICK HERE).

Study in Mice Shows Genes May Be Altered Through Drug Repurposing:
Ali Djalilian and Mark Rosenblatt, University of Illinois Chicago, repurposed MEK inhibitors (a class of anti-cancer drugs) to treat an aniridia-like condition in mice. “Patients with aniridia can develop progressive loss of their corneal stem cells…Our research in the Corneal Regenerative Medicine Laboratory is aimed at regenerating healthy corneal cells, which we hope can help these and similar patients,” said Rosenblatt. In the mice, the drug administration enhanced PAX6 gene expression, which normalized eye development and resulted in clearer corneas. To read this University of Illinois Chicago news story (CLICK HERE).

Zika Virus Affects Eye Development Before but Not After Birth:
Glenn Yiu, California National Primate Research Center, and colleagues reported that Zika infection during the first trimester of pregnancy can impact retinal development; however, the virus does not appear to affect ocular growth postnatally. The virus is primarily transmitted by the bite of an infected mosquito. However, it can also be passed through sexual contact, blood transfusions, organ transplants, and between mother and baby during pregnancy. “It has been known that congenital infection with the Zika virus can lead to eye defects, but it was unclear if the virus continues to replicate or affect eye development after birth,” Yiu said. “Our study in rhesus monkeys suggests that the virus primarily affects fetal development during pregnancy, but not the growth of the eye after birth,” said Yiu. To read this University of California, Davis news story (CLICK HERE).

New Approach Reveals Structure and Function of Individual Synapses:
Benjamin Scholl, Connon Thomas, and their colleagues at the Max Planck Florida Institute for Neuroscience reported a novel approach to measure the strength of connections between neurons. The team used light microscopy to visualize the activity of a population of synapses and electron microscopy to evaluate structural details of synapses. “Combining both structural and functional measurements of neurons provides a more holistic understanding of how our brains compute information,” said Thomas. To read this Max Planck news story (CLICK HERE).

Researchers Discover Clue to How to Protect Neurons and Encourage Their Growth:
Derek Welsbie, University of California San Diego, and collaborators identified a family of enzymes whose inhibition protects neurons while also permitting the regeneration of axons—projections that conduct signals between cells. Until now, there have been no effective methods to modify genes to improve both the long-term survival of neurons and promote regeneration. The finding could help efforts to develop therapies for neurodegenerative diseases like Alzheimer’s disease and glaucoma. To read this University of California San Diego story (CLICK HERE).

COVID-19 Found in the Cornea: Are Transplants a Transmission Risk?:
Shahzad Mian, University of Michigan, and colleagues analyzed the prevalence of COVID-19 in human post-mortem ocular tissues. They found that the virus can infiltrate corneal tissue, raising concerns that the disease could be transmitted to corneal transplant recipients. To read this University of Michigan news story (CLICK HERE).

Surgical and Drug Treatment Options Lead to Similar Outcomes for Diabetic Eye Disease:
Adam Glassman (Jaeb Center for Health Research), Jennifer Sun (Harvard University) and fellow researchers with the DRCR Retina Network reported data from a clinical trial that compared anti-vascular endothelial growth factor (VEGF) eye injections versus removal of blood via vitrectomy surgery and laser photocoagulation for proliferative diabetic retinopathy—the growth of new, abnormal blood vessels in the light-sensing retina. Both treatments improved central vision for the majority of participants, although approximately one-third of the participants needed both anti-VEGF injections and surgery. To read this NEI news story (CLICK HERE).

Cataract Surgery in Infancy Increases Glaucoma Risk:
Scott Lambert, Stanford University, and colleagues revealed that children who undergo cataract surgery as infants have a 22% risk of glaucoma 10 years later, whether or not they receive an intraocular lens implant. The findings come from the NEI-funded Infant Aphakic Treatment Study, which published 10-year follow-up results in JAMA Ophthalmology. To read this NEI news story (CLICK HERE).

NIH Researchers Discover Brain Area Crucial for Recognizing Visual Events:
Richard Krauzlis, senior NEI investigator, and collaborators found that a brain region in the superior temporal sulcus is crucial for processing and making decisions about visual information. The findings, which could provide clues to treating visual conditions from stroke, appear in Neuron. To read this NEI news story (CLICK HERE).

Hydrogel Could Open New Path for Glaucoma Treatment Without Drugs or Surgery:
C. Ross Ethier, Georgia Tech, and colleagues have developed a potential glaucoma treatment that could replace daily blood-pressure lowering eye drops and/or surgery. A gel-forming biodegradable polymer is injected just below the eye’s surface to enhance the release of aqueous fluid. According to a report on their research in rabbits, one injection reduced intraocular pressure for 4 months. A challenge to glaucoma treatment is patients forgetting to put drops in their eyes. “We believe the injection could be done as an office procedure during routine exams that the patients are already getting. Patients may not need to do anything to treat their glaucoma until their next office visit,” said Ethier. To read this Georgia Tech news story (CLICK HERE).

Problems With Depth Perception Caused by too Many Cells:
Z. Josh Huang, Cold Spring Harbor Laboratory, and colleagues demonstrated the importance of brain-cell pruning to binocular vision. Animals, including humans, kill off brain cells after birth through a pruning process called apoptosis. Based on experiments in mice, Huang reported that preventing apoptosis of chandelier cells in the brain’s visual cortex impairs depth perception. Huang said that reducing chandelier cell number likely frees cells in the binocular region of the visual cortex to communicate more efficiently between the two visual hemispheres, which is essential for rapidly integrating signals relayed from both eyes. To read this Cold Spring harbor Laboratory news story (CLICK HERE).