#Autophagosomes

[humancelltournament]

Human Cell Tournament Round 1

Propaganda!

An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, invading microorganisms). After formation, autophagosomes deliver cytoplasmic components to the lysosomes. The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane.

Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes. The function of beta cells is primarily centered around the synthesis and secretion of hormones, particularly insulin and amylin. Both hormones work to keep blood glucose levels within a narrow, healthy range by different mechanisms. Insulin facilitates the uptake of glucose by cells, allowing them to use it for energy or store it for future use.

[whats-in-a-sentence]

Electron micrographs of plant autophagosomes and autophagic bodies are shown in Figure 22.5.

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[blog-for-communications]

Volker Lannert - Universität Bonn Krafttraining aktiviert die zelluläre Müllabfuhr, was unverzichtbar ist, um die Muskulatur langfristig zu erhalten. Das hat ein Forschungsteam um die Universität Bonn gezeigt.

Krafttraining aktiviert zelluläre Müllentsorgung

Bonn, 23.08.2024. In unserem Körper ist die Entsorgung beschädigter Zellbestandteile unerlässlich für die Aufrechterhaltung von Geweben und Organen. Ein internationales Forschungsteam unter der Federführung der Universität Bonn hat nun wesentliche Einblicke in die Regulation eines beteiligten Entsorgungssystems erzielt. Demnach wird dieses durch Krafttraining aktiviert. Die Befunde könnten die Grundlage für neue Therapien gegen Herzversagen und Nervenerkrankungen bilden und auch zum Gelingen bemannter Weltraummissionen beitragen. Die Ergebnisse werden in der aktuellen Ausgabe des Fachmagazins "Current Biology" vorgestellt.

Muskeln und Nerven sind langlebige Hochleistungsorgane, deren zelluläre Bestandteile einem ständigen Verschleiß unterliegen. Bei der Entsorgung beschädigter Bestandteile spielt das Protein BAG3 eine entscheidende Rolle. Es erkennt beschädigte Komponenten und sorgt dafür, dass diese von zellulären Membranen umschlossen werden: Ein sogenanntes Autophagosom entsteht. In diesem „Müllbeutel“ wird der zelluläre Abfall gesammelt und schließlich für ein Recycling zerkleinert. Das Forschungsteam um Prof. Dr. Jörg Höhfeld vom Institut für Zellbiologie der Universität Bonn hat nun gezeigt, dass BAG3 in der Muskulatur durch Krafttraining aktiviert wird. Für die zelluläre Müllabfuhr ist dies wichtig, denn: Erst aktiviertes BAG3 bindet beschädigte Zellbestandteile effizient und treibt die Membranumhüllung voran. Ein aktives Entsorgungssystem wiederum ist unverzichtbar, um die Muskulatur langfristig zu erhalten. „Eine Beeinträchtigung des BAG3-Systems führt in der Tat zu rasch-fortschreitenden Muskelschwächen bei Kindern und zum Herzversagen, eine der häufigsten Todesursachen in westlichen Industrienationen“, erklärt Prof. Höhfeld.

Wichtige Erkenntnisse für Training und Rehabilitation

Sportphysiologen der Deutschen Sporthochschule Köln und der Universität Hildesheim waren maßgeblich an der Studie beteiligt. Der Hildesheimer Professor Sebastian Gehlert betont die Bedeutung der Befunde: "Wir wissen nun, welche Trainingsintensität für eine Aktivierung des BAG3-Systems nötig ist. Das hilft uns, Trainingsprogramme für Spitzensportler zu optimieren und den Muskelaufbau bei Patienten im Zuge der Rehabilitation zu verbessern." Gehlert nutzt diese Erkenntnisse auch bei der Betreuung von Mitgliedern des deutschen Olympiateams.

Nicht nur in Muskeln notwendig

Aber das BAG3-System ist nicht nur in der Muskulatur aktiv. Mutationen in BAG3 können auch zu einer Nervenerkrankung führen, die nach ihren Entdeckern als Charcot-Marie-Tooth-Syndrom bezeichnet wird. Dabei kommt es zu einem Absterben von Nervenfasern in Armen und Beinen. Betroffene können in der Folge Hände und Füße nicht mehr bewegen. Anhand von Zellen, die von Erkrankten stammen, zeigt das Forschungsteam nun, dass es bei bestimmten Formen des Syndroms zu einer fehlerhaften Regulation des BAG3-Entsorgungssystems kommt. Die Befunde belegen somit die weitreichende Bedeutung des Systems für die Gewebeerhaltung.

Unerwartete Regulation weist Weg für Therapien

Eine Überraschung erlebten die Forschenden, als sie die Aktvierung von BAG3 genauer untersuchten. „Viele Proteine werden in der Zelle durch die Anheftung von Phosphatgruppen, die sogenannte Phosphorylierung, aktiviert. Bei BAG3 ist der Vorgang jedoch umgekehrt“, so Jörg Höhfeld, der auch Mitglied im Transdisziplinären Forschungsbereich (TRA) „Life and Health“ der Universität Bonn ist. „In der ruhenden Muskulatur ist BAG3 phosphoryliert und die Phosphatgruppen werden bei der Aktivierung entfernt.“ Damit rücken die Phosphatasen – Enzyme, die die Phosphatgruppen entfernen – in den Mittelpunkt des Interesses. Bei der Identifizierung der Phosphatasen, die BAG3 aktivieren, kooperiert Höhfeld mit der Chemikerin und Zellbiologin Prof. Maja Köhn von der Universität Freiburg. "Die Identifizierung der beteiligten Phosphatasen ist ein wichtiger Schritt", erläutert Köhn. "Es erlaubt uns dann Wirkstoffe zu entwickeln, die auf die Aktivierung von BAG3 im Körper Einfluss nehmen könnten." Damit böten sich gegebenenfalls neue Möglichkeiten zur Behandlung von Muskelschwächen, Herzversagen und Nervenerkrankungen.

Auch für die Raumfahrt bedeutsam

Die Deutsche Forschungsgemeinschaft unterstützt die Arbeiten am BAG3-System im Rahmen einer Forschungsgruppe unter der Leitung von Prof. Höhfeld. Eine Förderung erhält Höhfeld aber auch von der Raumfahrtagentur im Deutschen Zentrum für Luft- und Raumfahrt: "BAG3 wird unter mechanischer Kraft aktiviert. Aber was passiert, wenn die mechanische Stimulierung ausbleibt? Zum Beispiel bei Astronautinnen und Astronauten unter Schwerelosigkeit oder bei immobilisierten und beatmeten Intensivpatientinnen und -patienten?“ erklärt Höhfeld. Die ausbleibende mechanische Stimulierung führt in diesen Fällen zu einem schnellen Verlust der Muskulatur. Höhfeld geht davon aus, dass die fehlende Aktivierung von BAG3 dabei den Muskelverlust vorantreibt. Auch in diesen Fällen könnten Medikamente hilfreich sei, um BAG3 zu aktivieren. Um dies zu klären, bereitet Höhfelds Team unter anderem Experimente an Bord der internationalen Raumstation ISS vor. Die Forschungen zu BAG3 könnten von daher eines Tages dazu beitragen, den Mars zu erreichen.

Förderung und beteiligte Institutionen

Neben der Universität Bonn sind die Universität Freiburg, die Deutsche Sporthochschule, das Forschungszentrum Jülich, die Universität Antwerpen sowie die Universität Hildesheim an der Studie beteiligt. Sie wurde gefördert von der Deutschen Forschungsgemeinschaft und der Raumfahrtagentur im Deutschen Zentrum für Luft- und Raumfahrt.

Originalpublikation:

Ottensmeyer, et al.: Force-induced dephosphorylation activates the cochaperone BAG3 to coordinate protein homeostasis and membrane traffic. „Current Biology“, DOI: 10.1016/j.cub.2024.07.088; https://doi.org/10.1016/j.cub.2024.07.088

Beitrag zum Blog

Bewegung ist Ausdruck nonverbaler Kommunikation. Technologische Entwicklung und Fortschritt begünstigen das Menschen sich zukünftig weniger Bewegen. Es benötigt daher den freien Wunsch, Willen und Antrieb von Menschen sich bewegen zu wollen. Motivation dafür zu finden. Raus aus der Unterdrückung, rein in ein Selbstbestimmtes Leben gehört zu den Themegebieten des Blogs. Sport, Mode, Smarte Textilien und damit auch Künstliche Intelligenz, in Auswirkung für das Individuum und seiner Teilhabe an der Bildung zur Gesellschaft, sowie als Ausdrucksmittel tiefliegender Kommunikation (Interozeption - Körpersignale aus dem Inneren.)

[yeast-papers]

TgATG9 is required for autophagosome biogenesis and maintenance of chronic infection in Toxoplasma gondii

BioRxiv: http://dlvr.it/T9PDLv

[leedsomics]

Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy

Autophagy is a constitutively active catabolic lysosomal degradation pathway, often found dysregulated in human diseases. It is often considered to act in a cytoprotective manner and is commonly upregulated in cells undergoing stress. Its initiation is regulated at the protein level and does not require de novo protein synthesis. Historically, autophagy has been regarded as non-selective; however, it is now clear that different stimuli can lead to the selective degradation of cellular components via selective autophagy receptors (SARs). Due to its selective nature and the existence of multiple degradation pathways potentially acting in concert, monitoring of autophagy flux, i.e. selective autophagy-dependent protein degradation, should address this complexity. Here, we introduce a targeted proteomics approach monitoring abundance changes of 37 autophagy-relevant proteins covering process-relevant proteins such as the initiation complex and the ATG8 lipidation machinery, as well as most known SARs. We show that proteins involved in autophagosome biogenesis are upregulated and spared from degradation under autophagy inducing conditions in contrast to SARs. Classical bulk stimuli such as nutrient starvation mainly induce degradation of ubiquitin-dependent soluble SARs and not of ubiquitin-independent, membrane-bound SARs. In contrast, treatment with the iron chelator deferiprone leads to the degradation of ubiquitin-dependent and -independent SARs linked to mitophagy and reticulophagy/ER-phagy. Our approach is automatable and supports large-scale screening assays paving the way to (pre)clinical applications and monitoring of specific autophagy fluxes. http://dlvr.it/T4lDvt

[myhamartiaishubris]

Influenza A M2 protein: nuh uh

Autophagosome about to fuse with a lysosome: fym nuh uh

[science-selected-yura15cbx]

Mammalian autophagosomes form from finger-like phagophores

[xiaoxiaodeshijie]

What are the anti-aging ingredients in skincare?

Many years ago, a seminal article titled "The Hallmarks of Aging" was published in the prestigious journal "Cell." This article systematically reviewed the classic features and indicators involved in the aging process of the human body. How were these features selected? The authors believed that they should reflect the normal aging process and be universally applicable. Additionally, they could be validated through experiments by demonstrating that exacerbating a specific indicator accelerated aging, while inhibiting it improved aging. This article also introduced a classic image that many of you who have attended lectures may be familiar with.

However, in 23 years, the author updated their article. Similarly, this enhanced version of the article was published in "Cell." In the updated article, the nine hallmarks of aging were expanded to twelve. They are as follows: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, and the newly added features of macroautophagy dysfunction, chronic inflammation, and dysbiosis.

Autophagy

also known as "self-eating," is a process where cells can degrade and recycle themselves when they age or experience dysfunction. If the clearance of these old cell waste materials is impaired, it can lead to accelerated aging. Previous studies have examined autophagy markers in tissues of long-lived individuals and found higher activity levels compared to the average population. This suggests that promoting autophagy can have anti-aging effects.

Which ingredients can promote autophagy?

For example, Viicode's niacinamide system can promote skin autophagy and accelerate the degradation of glycated proteins. Another ingredient from Viicode, a plant extract, can also activate cellular autophagy, allowing the skin to undergo its own "clean-up" process and degrade detrimental molecules within proteins.

Another example is the raw rice fermentation filtrate from HuaXi Biologics. This filtrate can promote the formation of autophagosomes and enhance the potential of cellular autophagy. Therefore, this ingredient is also considered an anti-aging component.

chronic inflammation.

Inflammatory aging, also known as inflammaging, is a popular concept in anti-aging research in recent years. In simple terms, as we age, inflammatory factors increase and further contribute to the acceleration of aging is closely, the. Conversely,If there is chronic inflammation present, it can also lead to premature aging. Moreover, the chronic inflammatory environment is closely related to other aging characteristics, and they are intertwined with each other.

Interventions targeting inflammation and the immune aging. Moreover system can help slow down the aging process to some extent.

What are some examples of combating inflammatory aging?

In terms of ingredients, many molecules with anti-inflammatory and soothing effects also have a certain impact on aging. For example, commonly seen extracts such as Centella asiatica extract, purslane extract, magnolol, and others have the ability to counteract inflammatory microenvironments and fight against aging.

the gut microbiota.

Regulating the gut microbiota is indeed another pathway for anti-aging. The gut microbiota can send signals to the peripheral nervous system, central nervous system, and other distant organs, exerting a strong influence on the overall health of the host. Disruption of this bidirectional bacteria-host communication can lead to ecological imbalance and various pathological conditions, including aging. We often refer to the "gut-brain-skin axis," which highlights the interconnectedness of the brain, gut, and skin. When one's mood is not well, it can lead to gastrointestinal disorders and manifest as skin issues. Similarly, disturbances in the gut microbiota can cause mental discomfort and frequent skin problems. We now understand that the skin microbiota plays a significant role in skin health, and likewise, the gut ecosystem is closely related to the skin.

In terms of intervention measures, consuming probiotic products orally can help improve gut ecology. Common examples include Lactobacillus bifidus, Bifidobacterium lactis, and Lactobacillus acidophilus. Additionally, certain prebiotic ingredients like inulin also provide benefits for the gut.

[bunnikida]

Okok I'm gonna read a bit more info abt autophagosome inhibition nd then I'm gonna sleep. I didn't do anything productive today but I'm not really retaining any information either

[pebblegalaxy]

The Emerging Mechanisms and Functions of Microautophagy: Understanding the Cellular Process and Its Potential Therapeutic Applications

Microautophagy is a cellular process that has recently garnered much attention among researchers due to its critical role in maintaining cellular homeostasis. It is a lysosomal degradation pathway that differs from the classical macroautophagy pathway in its mechanism and cargo selection. Unlike macroautophagy, where cytoplasmic cargo is engulfed by double-membrane autophagosomes, microautophagy…

[rnomics]

Genes, Vol. 14, Pages 512: Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle

In aquaculture, many stressors can negatively affect growth in teleosts. It is believed that cortisol performs glucocorticoid and mineralocorticoid functions because teleosts do not synthesize aldosterone. However, recent data suggest that 11-deoxycorticosterone (DOC) released during stress events may be relevant to modulate the compensatory response. To understand how DOC modifies the skeletal muscle molecular response, we carried out a transcriptomic analysis. Rainbow trout (Oncorhynchus mykiss) were intraperitoneally treated with physiological doses of DOC in individuals pretreated with mifepristone (glucocorticoid receptor antagonist) or eplerenone (mineralocorticoid receptor antagonist). #RNA was extracted from the skeletal muscles, and cDNA libraries were constructed from vehicle, DOC, mifepristone, mifepristone plus DOC, eplerenone, and eplerenone plus DOC groups. The #RNA-seq analysis revealed 131 differentially expressed transcripts (DETs) induced by DOC with respect to the vehicle group, mainly associated with muscle contraction, sarcomere organization, and cell adhesion. In addition, a DOC versus mifepristone plus DOC analysis revealed 122 DETs related to muscle contraction, sarcomere organization, and skeletal muscle cell differentiation. In a DOC versus eplerenone plus DOC analysis, 133 DETs were associated with autophagosome assembly, circadian regulation of gene expression, and regulation of transcription from #RNA pol II promoter. These analyses indicate that DOC has a relevant function in the stress response of skeletal muscles, whose action is differentially modulated by GR and MR and is complementary to cortisol. https://www.mdpi.com/2073-4425/14/2/512?utm_source=dlvr.it&utm_medium=tumblr

[yeast-papers]

The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy/nucleophagy cargos in fission yeast

Pubmed: http://dlvr.it/SzMxRS

[currentsinbiology]

Tiny helpers that clean cells

During the process of autophagy, damaged cellular components, unused proteins and other cellular waste are incorporated into a vesicle, called the autophagosome, rather like how domestic waste is packed up in bin bags. In mammals the vesicles are transported to a lysosome, or in yeasts and plants to vacuoles, the cell organelles. These organelles have a similar function to a recycling plant: they decompose the materials included with the autophagosomes, so that the individual components can be reused. Numerous proteins initiate and regulate the process in the cells: more than 40 different types have already been identified. However their molecular functions are still largely unknown. Also, until now it has not been understood how the autophagosomes fuse with vacuoles so that the cellular waste can be recycled.

Levent Bas, Daniel Papinski, Mariya Licheva, Raffaela Torggler, Sabrina Rohringer, Martina Schuschnig, Claudine Kraft. Reconstitution reveals Ykt6 as the autophagosomal SNARE in autophagosome–vacuole fusion. The Journal of Cell Biology, 2018; jcb.201804028 DOI: 10.1083/jcb.201804028

Cellular waste (magenta) is engulfed by autophagic membranes (green) in a yeast cell, monitored by live-cell fluorescence microscopy.Credit: Claudine Kraft

[bpod-bpod]

Bite Wound

To re-build, life must first clean away. Here, a fruit fly (Drosophila) embryo heals damage to one of its cells. The debris is eaten away by a recycling process known as autophagy, but the careful destruction doesn’t stop there. Researchers find structures called autophagosomes (orange) help to bite holes in the membranes of surrounding cells (green), which then join to form a syncytium – a sort of collaborate cell which plugs the gap in the tissue. Autophagy, and proteins involved such as TORC-1, may use syncytia to form stronger protective membranes around the sites of healing wounds. There are similar cells in developing muscles, and with increasing frequency as we age. With the partnership between clearing away and building in their minds, the team are now looking at how autophagy helps to renew and refresh membranes at different stages of life.

Written by John Ankers

Video from work by Parisa Kakanj and colleagues

Institute for Genetics, University of Cologne, Cologne, Germany

Video supplied by and copyright held by the authors

Published in The EMBO Journal, March 2022

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[themedicalstate]

How Autophagy Works

Self-digestion is critical to freeing up nutrients and guiding development, among other functions.

Autophagy—the process by which a cell digests and recycles various molecules and organelles in its cytoplasm—is critical for maintaining homeostasis and for helping cells survive low-nutrient conditions. In a series of steps, a vesicle precursor, known as the phagophore, is formed, and cellular contents accumulate as it matures into an autophagosome. Then, after fusion with a lysosome, the inner vesicle of the autophagosome is digested along with the cargo, and the products are released into the cytoplasm. Over the past 25 years, researchers have detailed the molecular regulators of this process, with recent insights shedding light on autophagy’s link to both health and disease.

1. Phagophore nucleation

A protein kinase complex and a lipid kinase complex coordinate the recruitment of a piece of membrane that will form the basis of the phagophore. The origin of the donor membrane is unknown, but may include the endoplasmic reticulum (ER), the Golgi apparatus, or the plasma membrane.

2. Phagophore expansion

With the help of several autophagy-related (ATG) proteins, a small, ubiquitin-like protein called LC3 (LC3-II when bound) binds the nascent phagophore to direct its expansion around cytoplasmic components to be degraded—which may be randomly selected or may include specific cargo such as damaged organelles or misfolded proteins, depending on the nature of the stress. ATG9 is a transmembrane protein that shuttles between the site of phagophore formation and peripheral membrane sites and is thought to recruit more membrane for the expanding phagophore.

3. Autophagosome formation

The elongating phagophore closes to form the double-membrane autophagosome, enclosing cytoplasmic cargo targeted for degradation.

4. Autophagosome-lysosome fusion

The outer membrane of the autophagosome fuses with the membrane of the lysosome, leading to the exposure of the cargo-enclosing inner autophagosomal membrane to the hydrolases present in the lysosomal lumen. This lysosome is now called an autolysosome.

5. Degradation and efflux

Lysosomal hydrolases degrade the inner autophagosomal membrane, and then the cargo within. Transporters known as permeases on the autolysosome membrane then move the macromolecules generated into the cytoplasm, where they can be reused by the cell.

By Vikramjit Lahiri and Daniel J. Klionsky (The-Scientist). Image: N.R.FULLER, SAYO-ART LLC.

[uicscience]

UIC researchers find evidence of possible link between herpes simplex and neurogenerative diseases

A new study by researchers at University of Illinois Chicago suggests that when the protein optineurin, or OPTN, is present in cells it restricts the spread of HSV-1, the herpes simplex virus type 1.

In a “first of its kind” study, researchers also found a potential direct connection between neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), glaucoma, and the herpesvirus, said Dr. Deepak Shukla, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye, and vice chair for research at UIC.

The research paper, “OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection,” led by Shukla, was published recently in the journal Nature Communications.

Researchers sought to discover why HSV-1 can become fatal for individuals who are immunocompromised but not for healthy individuals. Herpesviruses naturally infect the central nervous system and can result in degenerative brain and eye disorders, as well as encephalitis. However, in most individuals, the virus is suppressed during a primary infection before it can significantly damage the central nervous system.

The new research suggests why HSV-1 is suppressed: OPTN, a conserved autophagy receptor, selectively targets HSV-1 proteins to degradation by autophagy, explained Tejabhiram Yadavalli, a co-author of the study and visiting scholar at UIC’s department of ophthalmology and visual science.

“OPTN stops the virus from growing and it stops it by autophagy — engulfing the virus particles inside tiny vesicles called autophagosomes. The autophagy that happens is very selective. That has meaning for other viruses as well,” Shukla said.

The researchers believe the results from this study will apply to all eight different human herpesviruses.

For the study, mice with removed OPTN genes were infected with ocular HSV-1. The virus growth was much higher in the brains of animals without OPTN, killing local neurons and eventually leading to animal death. This shows there is a faster degeneration of neurons when OPTN is not there. Additional studies are being planned to examine naturally occurring mutations in OPTN, such as the ones reported in glaucoma and ALS patients, and how they may affect neuronal health and HSV-1 infection, Shukla explained.

“Where you have mutated OPTN plus herpes, you have the recipe to create a disaster in terms of neurodegeneration,” Shukla said.

“The study also shows there is an impairment of immune response when there is a deficiency in OPTN.  OPTN is needed to signal an influx of proper immune cells at the site of infection. When you don’t have it, you have issues,” said Chandrashekhar Patil, also a co-author of the study and a visiting scholar at UIC’s department of ophthalmology and visual science.

Some of those issues could include neurodegenerative disorders, which researchers believe further research may show.

“We think we will have data to show other viruses, such as Epstein-Barr, Kaposi’s sarcoma, varicella-zoster, are all going to share this mechanism because they share homologous proteins,” Shukla said.

Because the herpesvirus sits in neurons forever, there is speculation it is connected to neurodegenerative diseases. The immune system requires inflammation to constantly fight off the virus, and neurons have some degree of damage because of this continuous immune response, according to Dr. Tibor Valyi-Nagy, professor of pathology, director of neuropathology at UIC and research collaborator on the study.

The study also showed that animals without OPTN and infected with HSV-1 after 30 days lost the ability to recognize objects. Shukla said this could be an indication that having HSV-1 along with a mutation of OPTN could accelerate neuronal damage, which would translate into cognitive impairment.

“Part of our translational research can be how can we correct the problems with OPTN so that we don’t have issues with neurodegeneration,” Shukla said.

Additional authors are Joshua Ames, Rahul Suryawanshi, James Hopkins, Alexander Agelidis, Chandrashekhar Patil and Brian Fredericks, all of UIC, and Henry Tseng of Duke University Medical Center.

This research was supported by the National Institutes of Health and National Eye Institute grants (K08-EY021520-02, RO1 EY029426, P30 EY001792 and RO1 EY024710) as well as the Butner Pioneer Award, Duke Health Scholars and Research to Prevent Blindness unrestricted funds.