Title - Extracellular Vesicles in the Eye: From cellular communicators to biomarkers and therapeutics (GL)

Contributing section (s): AP, BI, PH, RE, RC

Organizer (s): Paloma B. Liton.

Speaker (s): Mikael Klingeborn, Miguel Flores-Bellver, Stanislav Tomarev, Fiona McDonnell, Yutao Liu, and Julia Busik.

Description: Extracellular vesicles (EVs), including exosomes and microvesicles, are membranous nanovesicles that contain bioactive cargo molecules derived from the cell of origin. These EVs act as signaling messengers, carrying the cargo through the body and orchestrating systemic responses. Recent studies in different animal models have shown the capability of EVs to promote wound healing and reverse disease states. EVs have been also shown to serve as biomarkers in a variety of human diseases. The purpose of this meeting is to disseminate the latest discoveries regarding the basic biology and clinical utility of EVs. In particular, the minisymposium will explore the role of EVs in ocular human diseases, therapeutic approaches, and biomarker discoveries. The meeting will additionally cover new methodologies, tools, and technologies for studying EVs, to enable further advancements in the characterization of EV processes and facilitate translational impact into diagnostic and therapeutic applications. By integrating research in basic science with clinical perspectives, this meeting will foster cross-disciplinary discussions and collaborations to drive the field forward toward medical impacts. This session will collectively summarize all the latest developments in microvesicle biology and therapeutics in ocular tissues.


Title: Epigenetic landscape in ocular health and disease (BI)

Contributing section (s): RE, RC, GEN

Organizer (s): Stephanie Hagstrom, Robert Hufnagel, and Elena Semina.

Speaker (s): Elfride De Baere, Tom Reh, Anand Swaroop, Michael Dyer, and Ayellet Segrè.

Description: Epigenetic modifications are heritable alterations in the chemical structure of DNA, including DNA methylation, histone modification and various RNA-mediated processes, that do not change DNA sequence but affect gene expression. Cumulatively, epigenetic modifications form the so-called epigenetic landscape where some genes are actively expressed while others are suppressed. Epigenetic analyses into the roles of these modifications in the development, aging and regeneration of ocular tissues are in their early stages but already provided promising results with a potential to improve early diagnostic strategies and therapeutic options for ophthalmic disorders. This session will discuss modern approaches and some of the most important findings in the field of ocular epigenetics.


Title: RPE heterogeneity in health and disease (BI)

Contributing section (s): RE, RC

Organizer (s): Stephanie Hagstrom, Robert Hufnagel, and Elena Semina.

Speaker (s): John Nickerson, Christine Curcio, Davide Ortolan, Robert Mullins, and Patsy Nishina.

Description: Understanding regional differences in the RPE monolayer has been an uncharted area despite the evidence of heterogeneous RPE degeneration in specific retinal diseases. For example, choroideremia and late-onset retinal degeneration lead to peripheral RPE loss. In contrast, age-related macular degeneration affects central vision and causes the loss of macular RPE cells. Morphometrically, RPE size differs in human RPE flatmounts, with central cells being smaller and mid-peripheral cells larger. Structurally, RPE cells have either finger or petal-like apical processes to interact with rods or cones, respectively; and molecularly, RPE from the central or peripheral part of the retina show differences in gene expression and lysosomal activity. Efforts to shed light on RPE heterogeneity will help understand the molecular mechanisms of regional differences. This knowledge will change the current understanding of disease progression and will lead to the development of precise therapeutics for retinal degeneration. We aim to combine studies from different model systems and share recent advancements in the field.


Title: ‘Diversity’ through the Human Eyes by Computer Vision (CL)

Contributing section (s): MOI

Organizer (s): Ching-Yu Cheng.

Speaker (s): Ching-Yu Cheng, Alejandro F. Frangi, Cecilia S. Lee, Yun Liu, Pearse Keane, and Emily Chew.

Description: The human eye is considered a platform to study a variety of systemic diseases. Computer vision, which enables computers to derive information from images, possesses potential power to screen or risk stratify various systemic disorders based on ocular images. Leading research targets in this field include pressing population health issues, such as cardiovascular diseases, diabetes, Alzheimer diseases, chronic kidney diseases, and aging etc. In this symposium, we will introduce the latest developments in the field o image-based oculomics by using computer vision, and discuss lessons and challenges from dataset curation to clinical deployment.


Title: Emerging Therapeutics to Maintain Corneal Health (CO)

Contributing section (s): IM

Organizer (s): Vishal Jhanji, Pedram Hamra, and Kyung Chul Yoon.

Speaker (s): Nancy McNamara, Gary Hin-Fai Yam, David Eveleth, Deepak Shukla, Holly Rose Chinnery, Ruby Shalom-Feuerstein, and

Peter Y. Lwigale.

Description: The cornea is a highly specialized transparent tissue and the major refractive element of the eye. Corneal infections and injuries activate a cascade of events that either lead to the resolution of anatomical insults over time or, result in permanent damage in the form of corneal edema, neovascularization, haze, scarring, and limbal stem cell deficiency. The talks in this symposium will be focused on translational research and advances in therapeutics with the potential for clinical discoveries. The presentations will feature established scientists in the field of cell biology, pharmacology, and drug delivery.


Title: Mitochondrial optic neuropathies – from disease mechanisms to therapeutic strategies (EY)

Contributing section (s): EY

Organizer (s): Patrick Yu-Wai-Man.

Speaker (s): Jason Meyer, Valerio Carelli, Patrick Yu-Wai-Man, Michael Whitehead, and Guy Lenaers.

Description: Inherited optic neuropathies are an important cause of blindness in children and young adults with an estimated minimum prevalence of 1 in 10,000.  Remarkably, all of the causative genes identified to date impair mitochondrial function, directly or indirectly, driving the pathological cascade that eventually leads to retinal ganglion cells (RGCs) loss and optic nerve degeneration. The two classical mitochondrial optic neuropathies are Leber hereditary optic neuropathy (LHON) caused by pathogenic mitochondrial DNA mutations and autosomal dominant optic atrophy (DOA) caused by mutations in the nuclear-encoded OPA1 gene. A major challenge in understanding the mechanisms linking these genetic defects to the selective loss of RGCs is the lack of access to human tissues to study these particular cells, compounded by the limitations of existing animal models. To circumvent these difficulties, induced pluripotent stem cells (iPSCs) have been established from patients with LHON and DOA, and then differentiated into RGCs with the aim of replicating their native environment. In parallel, advances in gene delivery aimed at the mitochondrial compartment and mRNA-based therapeutics have opened up exciting new opportunities that will hopefully allow clinicians to improve the visual outcome for patients affected with mitochondrial optic neuropathies.


Title - Extracellular Vesicles in the Eye: From cellular communicators to biomarkers and therapeutics (AP)

Part II

Contributing section (s): AP, GL, RE, RC

Organizer (s): Vivian Lee, and Jesse Berry.

Speaker (s): Jesse Berry, Sophie X. Deng, Dimitrios Karamichos, Jessica N. Cooke Bailey, Sun Young Lee, Swathi Kaliki, and Liya Xu.

Description: Exosomes are membrane-bound extracellular vesicles with a diameter of 30 to 150 nm. They are secreted by virtually all types of cells and are present in virtually all biological fluids. Once assumed to be just waste material spewed out by cells, studies now show they participate in key cellular functions, such as cell-to-cell communication, and play important roles in various diseases, such as cancer and metabolic disorders. Studies have also started to explore the potential of exosomes for treating diseases, harnessing their innate messaging system for therapeutic purposes. However, exosomes have been historically difficult to study given their finickiest and elusiveness. Nevertheless, these small bubbles pack a punch, capable of enveloping potent cellular material in a vehicle that can travel anywhere and everywhere. The purpose of this two-part program is to inform seasoned and new investigators about this burgeoning field and its challenges. Part I will highlight the basic biology of exosomes while Part II will cover the translational potential of exosomes in the eye.


Title: Consequences of altered cell metabolism and/or mitochondrial functionality during ocular health and disease (IM)

Contributing section (s): CO, IM, RE, RC, VN

Organizer (s): Anthony St. Leger, Lynn Hassman, and Ashok Kumar.

Speaker (s): Wei Li, Danielle Robertson, David S. Williams, Renu Kowluru, Katherin Wert, and Anthony St. Leger.

Description: A great amount of effort has been invested in understanding how cellular metabolism dictates health and states of disease. Specifically, the decision of a cell to enter a glycolytic or respiratory state can determine whether a pathogen is eliminated, autoimmunity is resolved, or cancer is rejected. More recently, cellular metabolism has been investigated in the context of ocular surface and intraocular diseases. Furthermore, within the ocular environment, a central focus has been placed on the functionality of mitochondria within various populations of cells in the anterior and posterior portions of the eye. This symposium will cover topics about cell metabolism and mitochondrial function with a primary focus on ocular diseases and how viable treatment of dysfunctions within cellular metabolism processes may alleviate disease.


Title: Immune response in the anterior segment of the eye – lens, cornea, and anterior uveitis (LE)

Contributing section (s): CO, IM

Organizer (s): Juliet A. Moncaster, Catherine K. Cheng, and Xingjun Fan.

Speaker (s): Sue Menko, Jean X. Jiang, Daniel Saban, Claus Cursiefen, and Lynn Hassman.

Description: The eye is regarded as an immune-privileged site, however, it is now appreciated that immune cells play a central role in response to trauma and disease in the tissues of the eye, including the lens. The mechanisms underlying their function and response are not completely understood. Furthermore, newly defined immune cell subsets are emerging adding to the complexity of elucidating their role in health and disease. This Minisymposium will focus on the immune response in the anterior segment of the eye which is most proximal to the external environment and susceptible to infection, injury, and autoimmunity. It will provide our current knowledge on the role of immune cells in the anterior segment in health, trauma, and disease.


Title: Gene-independent therapeutic approaches for treatment of retinal disease (RC)

Contributing section (s): BI, GL, RE, RC

Organizer (s): Budd Tucker, and Jason Meyer.

Speaker (s): Connie Cepko, José-Alain Sahel, Jonathan H Ling, Adriana Di Polo, Adriana Di Polo, and Marina Gorbatyuk.

Description: AAV mediated gene augmentation is one of the most promising therapeutic approaches being developed for the treatment of recessive inherited retinal disease. Unfortunately, for patients with dominantly inherited gain of function disorders, or those with mutations in genes that are too large to be packaged into AAV vectors, alternate strategies are needed. For patients with dominant disease-causing mutations, knockdown and replacement of the gain of function alleles is being developed. For large genes novel CRISPR based strategies such as prime editing and split-intine mediated dual delivery followed by in vivo recombination are gaining traction. As promising as these new approaches are, each relies on the use of gene and/or mutation specific reagents for the treatment of a small patient population, making clinical trial and commercial development challenging. In this mini symposium we will explore some of the latest gene agnostic therapeutic approaches currently being developed. Specifically, strategies designed to prevent cell death by alleviating oxidative stress, maintaining cell viability by targeting pathway specific dysfunction, and restorative optogenetic approaches, will be discussed. By discussing the latest gene agnostic approaches, this mini symposium will stimulate new ideas to further advance the field toward development of global treatment strategies that can be used to treat larger patient populations.


Title: Novel models and approaches for cell replacement in retinal degeneration (RC)

Contributing section (s): GL, RE

Organizer (s): Jason Meyer, and Budd Tucker.

Speaker (s): Kapil Bharti, Dennis Clegg, Juliette McGregor, Jane Sowden, Brian Samuels, and

Thomas Johnson III.

Description: Stem cells can serve as a powerful tool for the replacement and regeneration of retinal cells that have been lost due to a variety of blinding diseases, including age-related macular degeneration and glaucoma. Human pluripotent stem cells, including both embryonic and induced pluripotent stem cells, are capable of differentiation into all of the major cell types of the retina, providing a virtually unlimited source for replacement applications. Numerous studies over the past several years have demonstrated some degree of feasibility for cellular replacement, and recent clinical trials in some conditions are highly encouraging. However, given the complexity of neural connections and important differences between traditional rodent models and human patients, a critical need exists for the establishment of novel models that more accurately represent human retinal degeneration, as well as novel approaches for the engraftment of transplanted cells. In this minisymposium, we will explore some of the latest strategies for cellular replacement, beginning with the replacement of RPE cells, and then proceeding to discussions about the replacement of photoreceptors and then retinal ganglion cells. We will address new methodologies for the differentiation and transplantation of donor cells, as well as novel animal models that are now being used to better mimic the human disease condition. By discussing the latest approaches for both engineering donor cells along with modulating the host retinal environment, this minisymposium will stimulate new ideas to further advance the field of cell replacement in the retina.


Title: Understanding Systemic Disease through Vascular Imaging (VI)

Contributing section (s): VI

Organizer (s): Jessica I. W. Morgan, and Brian Vohnsen.

Speaker (s): Stephen Burns, Toco Chui, Amir Kashani, Hong Jiang, Yuhua Zhang, and Sarah Mrejen.

Description: The optical elements of the eye provide a window through which the retinal and choroidal vasculature can be observed. Abnormal vasculature structure and disruptions in normal blood flow are markers of systemic disease. Thus, imaging of retinal and choroidal vasculature can provide insight to the state of systemic diseases such as hypertension, diabetes, sickle cell disease, and Alzheimer’s. Panelists in this session will describe current state-of-the-art techniques for imaging the retinal and choroidal vasculature and scientific findings related to applying these techniques to study systemic disease. The discussion will include future directions and remaining challenges for widespread use of ocular imaging technology in systemic disease. 


Title: Advances in retinal connectomics (VN)

Contributing section (s): VN

Organizer (s): Bryan William Jones.

Speaker (s): Crystal Sigulinsky, Rebecca Pfeiffer, Yeon Jin Kim, Mrinalini Hoon, and Will Grimes.

Description: Retinal connectomics is an emerging field that is redefining our understanding of the complexity of retinal circuit topology. Advancements in imaging and physiology in the field are influencing anatomy, physiology, and development across a variety of model systems from mouse to non-human primate and human. This proposed Minisymposium will highlight some of the latest advancements in the field.


Title: Cellular and genetic diversity in the retinas of human and non-human primates (VN)

Contributing section (s): VN

Organizer (s): Tiffany Schmdt, Christophe Ribelayga, and Christophe Ribelayga.

Speaker (s): Yirong Peng, EJ Chichilnisky, Frans Vinberg, Sara Patterson, and Michael Manookin.

Description: Cellular diversity and its impacts on visual processing are a fundamental question in visual neuroscience. Though the striking diversity of retinal neurons at the molecular, structural, and functional level is now well-established in rodent, fish, and other non-primate vertebrates, the extent of the cellular diversity in the retinas of human and non-human primates and whether or how it parallels that seen in other vertebrates have remained major open questions. Recent advances in genetic, physiological, and imaging technologies have allowed researchers to begin to probe these questions in the retinas both human and non-human primates, allowing for a deeper insight into the diversity and function of retinal cell types than ever before.