Through the Looking Glass - University of Pittsburgh Spring 2021 Alumni Newsletter

From the Desk of Dr. Conner

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s we finally thaw out from this exceptional winter, we have highlights to share from the UPMC Eye Center.

First, we are excited to announce a recent transformative gift to the Eye & Ear Foundation from the Henry L. Hillman Foundation that will help elevate the Department of Ophthalmology at the University of Pittsburgh into one of the largest and most innovative vision research centers in the world. We encourage you to read below about this important gift and the impact it will have on our Department.

Our research faculty continue to prosper with ongoing and new funding for projects to develop better understanding and treatment of infectious keratitis, corneal scarring, optic nerve degeneration and glaucoma, retinal degeneration, and novel drug delivery – you can read about these grants and the critical work that they support here.

We are also happy to share a recently announced collaboration with the FDA’s Center for Devices and Radiological Health that will provide a one-of-a-kind opportunity for our academic faculty to develop new treatments and rehabilitation strategies to help patients who are living with visual impairments. This 5-year commitment is expected to yield many innovations and help catapult our Department to even greater heights.

Ian Conner, MD, PhD

Our Department continues to make an impact on the scientific community at large with over 200 academic publications in 2020. Please visit the enclosed link to get a glimpse at all the projects our faculty have been working on.

For this issue’s alumni spotlight, we feature Dr. Sean Donahue, the Chief of Pediatric Ophthalmology at Vanderbilt University – among his many accolades. Dr. Donahue shares a few cherished memories of his career and his past time in Pittsburgh.

Finally, be sure to check out our most recent webinars with the Eye & Ear Foundation and remember to update us on your professional and personal milestones so that we may share them with your fellow alumni in future editions. We’d also love to have our alumni participate in our grand rounds presentations. If you’re interested in participating please reach out to Natalie Susany at susanynj@upmc.edu for more information.

All the best, Ian Conner, MD, PhD Chief of the Glaucoma Service Director, Glaucoma Fellowship Associate Program Director, Ophthalmology Residency Program UPMC Eye Center

In This Issue From the Desk of Dr. Conner

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$20 Million Gift from the Henry L. Hillman Foundation Advances Vision Research at the Department of Ophthalmology at the University of Pittsburgh 2 Grant Summaries

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Pitt Teams With FDA To Develop Therapies That Could One Day Restore Vision To Blind People

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2020 Department of Ophthalmology Publications

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Ophthalmology Alumni Spotlight

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Webinar Information

Back Cover

$20 Million Gift from the Henry L. Hillman Foundation Advances Vision Research at the Department of Ophthalmology at the University of Pittsburgh The Eye & Ear Foundation received a very generous and transformative $20 Million gift from the Henry L. Hillman Foundation to fund vision care research and development.

The Eye & Ear Foundation has now reached its halfway point in its campaign to support vision restoration breakthroughs, advance technologies and therapies addressing vision loss, lower barriers to healthcare for all Pittsburghers, and fuel the growth of the city’s burgeoning biotech sector.

The $20 million gift from the Henry L. Hillman Foundation, the Eye & Ear Foundation will fund vision care research and development.

This very generous and transformative gift has helped the Foundation reach its halfway point in its campaign and support vision restoration breakthroughs, advance technologies and therapies addressing vision loss, lower barriers to healthcare for all Pittsburghers, and fuel the growth of the city’s burgeoning biotech sector.

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Dr. José-Alain Sahel, who arrived at the University of Pittsburgh in 2016 from the Institut de la Vision at Sorbonne University, Paris, to direct the Department of Ophthalmology, will lead the vision work made possible by the Henry L. Hillman Foundation gift.

“We are driven by helping patients,” Sahel said. “It starts with identifying conditions among patients, which flows into using research to find solutions, creating new therapies and devices, commercializing those advancements, and ultimately bringing them back to the patient by enabling access to everyone.”

“No one person can do this,” he added.

“It takes teams of clinicians, scientists, educators, rehabilitation experts, and patients themselves, all looking at questions that have not been solved. Only then can you develop answers.”

Vision degeneration affects nearly everyone in one form or another as they age, and the number of individuals with visual impairments is expected to triple by 2050.

Pittsburgh, with its aging population, will be highly affected by this epidemic of vision loss. Finding cures for the most common eye ailments and solutions to rare diseases and impairment due to injury are equally important, Sahel said. His teams are working on nearly every aspect of blindness, from common conditions such as glaucoma and macular degeneration to regenerative therapies and engineering artificial retinas and the hardware and software that feeds them information.

Further supporting an equitable regional economy, the Hillman gift includes funding for vision-related workforce development— training local residents to fill jobs created by the overall project. It also provides seed funding for breakthrough research with

high potential for commercialization and emerging startups working in the sector.

“Dating back to the 1960s, the Henry L. Hillman Foundation has directed much of its attention to advancing quality of life in the region,” said Foundation President David Roger. “Pittsburgh stands in a unique position to lead the world in life sciences, and this grant will help shape a corridor that will drive the post-pandemic economy and create breakthrough discoveries—to the benefit of the region’s residents—for decades to come.”

The University of Pittsburgh already is investing heavily in growing life sciences

research and education, including bringing crucial faculty and staff to the UPMC Vision and Rehabilitation Tower, funded by UPMC, rising in Pittsburgh’s Uptown neighborhood.

create job and training opportunities for adjacent neighborhoods and the city with an emphasis on promoting equitable access to services and employment.

The Henry L. Hillman Foundation gift will, among other efforts, improve access to vision care for underserved communities through outreach and direct care; help build and staff a vision “street lab” to test new treatments and therapies in safe, controlled, virtual and real-life environments; and support research into breakthrough programs such as biomedical solutions to corneal blindness. The gift will also fund commercialization efforts and will, in turn,

This work requires a strategic alignment of facilities and resources, investment in specialized laboratories and leadership, and close coordination among key faculty, entrepreneurs, and community stakeholders. Through such partnership and investment, Southwestern Pennsylvania will become a hotbed for world-renowned patient access and care, new discoveries, and commercialization, area leaders say.

Construction continues on the new UPMC Vision and Rehabilitation Tower on the UPMC Mercy campus.

Construction is expected to be finished in late 2022/early 2023.

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Grant Summaries Dr. Morgan Fedorchak received a grant from Penn State University/NASA Pennsylvania Space Grant Consortium for her project entitled “Characterization and Modulation of Corneoscleral Drug Absorption in Acute Microgravity--Optimizing Ocular Health Against Spaceflight Associated Neuro-ocular Syndrome.” This funding will enable Dr. Fedorchak and her team to obtain preliminary data on corneal drug absorption under a variety of conditions at normal gravity. They will then use this data for comparing changes to drug absorption that occur in microgravity during parabolic flight. These studies will provide valuable insight for best practices to administer eye drop medication in space and deviations from expected dosing that may result during spaceflight.

Dr. Fedorchak also received a grant from the Cystinosis Research Foundation to develop a topical, controlled release cysteamine eye drop. Dr. Fedorchak and her team are continuing to develop a novel eye drop formulation for corneal cystinosis that will decrease dosing frequency from once per hour to once per day. Their prior work has shown success in delivering the necessary amount of drug and extending the shelf life from only one week to over seven weeks, and this most recent funding will allow for preclinical testing to enable upcoming clinical trials.

Dr. Gary Yam received a grant from the Eye Bank Association of America to study stromal cell-based therapy for corneal scarring. This study will investigate an innovative cell therapy approach in restoring healthy corneal stromal cells to reduce corneal scarring and to regenerate corneal stroma with normal functionality and visual function. The outcomes of this study will be instrumental in treating corneal opacities and could have a broad impact on the global shortage of donor tissue. The success of cell-based therapy will simplify treatment, making the therapy accessible to patients who currently do not have viable treatment options.

Dr. Leah Byrne received funding from UPMC Immune Transplant and Therapy Center and the E. Matilda Ziegler Foundation to develop gene therapies for retinal degeneration. This work will result in new approaches for efficient delivery of therapeutic genes and large genes to the retina, enabling gene replacement and genome editing for diseases including Usher1F.

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Grant Summaries (continued) Dr. Ian Sigal received a grant from the NIH to study optic nerve head microstructure, biomechanics and susceptibility to glaucoma. In this project we leverage imaging and analysis tools recently developed by our lab to characterize the optic nerve head. We analyze the tissue architecture, mechanical properties and biomechanical sensitivity to intraocular pressure. We evaluate how the tissues change with age, and how this affects its ability to support eye pressure. This work is towards our long-term objective of identifying properties of the eye that predict susceptibility to glaucomatous neural tissue damage before it occurs, at all ages and levels of pressure.

Dr. Ethan Rossi received NIH funding for his work on distinguishing normal aging from agerelated macular degeneration at the level of single cells in the living human eye. Dr. Rossi’s project aims to understand how retinal cells change in normal aging and how these normal age-related changes differ from the changes that lead to age-related macular degeneration.

This project will allow us to detect age-related macular degeneration earlier and will produce new tools to monitor retinal cells that will facilitate the development and testing of preventative therapies to slow or prevent vision loss in age-related macular degeneration.

Dr. Rob Shanks received a grant from the Dartmouth-Hitchcock Clinic for his research in determining the minimum dose of fungus to induce Keratitis. Dr. Shanks is working with the Charles T. Campbell Laboratory of Ophthalmic Microbiology on a pilot grant in partnership with an ophthalmologist (Michael Zegans, MD) and fungal expert (Robert Cramer, PhD) at the Geisel School of Medicine at Dartmouth to address the problem of fungal infections of the eye. Ocular fungal infections are a major problem world-wide. The goal of this pilot study is to develop a model with which we can evaluate new therapeutics to help in the fight against this blinding disease.

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Grant Summaries (continued) Dr. Jeff Gross received a grant from the BrightFocus Foundation for his work in identifying novel genes and pathways that protect RGCs from injury-induced death. Experiments in this grant utilize the zebrafish as a model system, leveraging its unique biology whereby RGCs do not die when their axons are damaged, even in extreme cases when the optic nerve is completely severed. By understanding how zebrafish RGCs survive after axonal damage, we will uncover novel modes of neuroprotection that could ultimately be translated into new targets for neuroprotection to preserve RGCs in glaucoma patients.

Dr. Paul “Kip” Kinchington received NIH funding to study the effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo. This award, led by Dr D’Auito of Psychiatry collaborating with Dr. Kinchington, extends their research into developing 3 dimensional models to study how the human herpesvirus HSV-1 (the cause of blinding stromal keratitis), interacts with host neurons to hide from immunity and then cause recurrent eye diseases, deadly encephalitis and cognitive decline.

Dr. Kinchington received another grant from the NIH to study small non-coding RNAs of VZV: role in lytic and latent infection. This project examines a set of small RNAs made by Varicella zoster virus 9VZV and if they can be therapeutic targets to prevent Herpes Zoster, the painful reactivated disease caused by this human herpesvirus. Most adults have VZV inside them in a latent form from when they got chickenpox as a child. Zoster can seriously damage vision and cause blindness when it develops on the head in older people.

Dr. Kinchington received an additional grant to research the role of the VLT RNAs in infection, reactivation and disease. This major five-year project in the study of Varicella Zoster virus (VZV) examines how an RNA found in the neurons of people latently infected with VZV contributes to the long dormant state between chickenpox and Herpes zoster. This appears to be the only product made by the virus during this long dormant state; if researchers can target it therapeutically, they may be able to block zoster and the eye disease it can cause.

Dr. Takaaki Kuwajima received a grant from the Eye & Ear Foundation/Louis J. Fox Center for Vision Restoration for his research on optic nerve regeneration.

The funded project is focused on the investigation of the neuroprotective and regenerative effects of a novel combination therapy of FDA-approved drug, statins and an ECM-based reagent, MBV in the rodent optic nerve injury model. When completed, his results could help to establish a practical and effective regenerative approach for treatments of ocular trauma in humans.

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Grant Summaries (continued) Dr. Susana da Silva received a grant from the ARVO Foundation/Genentech Age-related Macular Degeneration Research Fellowship to establish foveated 3D-retinal-organoids by spatio-temporally manipulating RA/FGF signaling during early organoid differentiation. The establishment of a model that closely simulates the human foveated retina is a must-needed initial step towards the subsequent creation of a AMD model that can greatly contribute to advance our fundamental understanding of the disease. Additionally, this scalable in vitro model system can immensely aid in the discovery of new treatments by allowing highthroughput drug screens, modeling of the different genetic factors associated with AMD, or simply serve as a reliable source of foveal specialized cells amenable for transplantation.

Dr. da Silva also received funding from the Knights Templar Eye Foundation for her research on the function and dysfunction of PAX6(+5a) in embryonic fovea development and foveal hypoplasia. Using newly developed methods for embryological in vivo gene manipulations and the chick retina as a model system we tested the role of PAX6(+5a) in fovea development and address how the R128C mutation identified in pediatric patients with IFH affects its function leading to foveal hypoplasia. This work advances our understanding of the fundamental molecular mechanisms underlying fovea formation and contributes to the development of newer therapies for treating congenital foveal hypoplasia conditions.

Dr. Yuanyuan Chen received a grant from the NIH for pharmacological studies of rhodopsin metabolism. Mutation of the RHODOPSIN gene causes an inherited visual disorder called retinitis pigmentosa. No effective treatment is currently available for this disease. The goal of this study is to understand the role of rhodopsin folding and metabolism in photoreceptor cell death by pharmacological approaches, so that we will develop effective drug candidates that prevent photoreceptor death by restoring rhodopsin homeostasis.

Dr. Chen also received a grant from the Eye & Ear Foundation, The Bruce & Barbara Entrepreneurial Research Award, for her research on the discovery of a novel, first-in-class endogenous, small molecule, potent and efficacious protective agent with restorative actions on retinal degenerative diseases. Photoreceptor death occurs in numerous blinding diseases including retinitis pigmentosa and age-related macular degeneration. Imbalance of purines contribute to oxidative stress and over-active retinal inflammation are common pathways contributing to photoreceptor death. This project is to study the pharmacodynamics and pharmacokinetics of a potent multi-tissue protecting agent in preventing photoreceptor death and restoring their morphology and function.

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Pitt Teams With FDA To Develop Therapies That Could One Day Restore Vision To Blind People

By Dr. Maria Simbra, CBS Pittsburgh

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PITTSBURGH (KDKA) — The University of Pittsburgh is collaborating with the Food and Drug Administration to help people with impaired vision.

The research will identify patient needs, difficulties and expectations while developing methods and measurements for assessing visual impairment.

Pitt’s Department of Ophthalmology has been developing cell therapies and gene therapies, optic nerve regeneration, prosthetic vision, and brain stimulation to restore sight.

when you go to school? And when you get older, what are the difficulties?” Dr. Sahel says. “You need to work with the patients to find what is useful and what is not useful.”

They will also work with innovators at Carnegie Mellon University.

“With all the technology available, that could be integrated into a smartphone but also headsets,” says Dr. Sahel.

Other departments will be helping, too — such as occupational therapy and rehabilitation

“We are really fighting blindness from many angles,” says Dr. Sahel. “We try to protect what is remaining in the retina, reactivate what is sleeping, replace what is lost with prosthetic cells, cell therapy, regenerate the optic nerve for people who have lost the optic nerve, or go directly to the brain to stimulate the brain when you’ve lost the rest of the system.”

The FDA will help with its existing collection of information about patient-reported outcomes.

“What happens when you drive? What happens when you go to work? What happens

2020 Department of Ophthalmology Publications Faculty in the Department of Ophthalmology published over 200 academic studies in 2020 across a variety of specialty areas. For a full list of publications by our faculty please visit HERE.

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services — because patients will need time and practice to get used to the new technologies.

“You need to teach people how to see again,” Dr. Sahel said. “Sometimes, impairment, visual impairment, is not just visual. There is also hearing impairment. There is balance impairment.”

Ophthalmology Alumni Spotlight Sean Donahue, MD, PhD

Best University of Pittsburgh memory:

City:

I really just have so many memories of my time with my colleagues in Pittsburgh.

Going our for pizza, wings, and beer with Brian Caputo, Brian DeBroff and others.

Going to Penguins games with George Buerger, along with the eggnog he would make for holiday parties. And also going to Pirates games with Brian Caputo and my young son Patrick.

Resident, 1990-1993

Brentwood, TN

Family: Married with four grown sons.

Hobbies: I am an avid runner and skier. I started running 20+ years ago and have run 17 full marathons, including Boston twice. I also enjoy downhill skiing in Colorado and Utah.

I also enjoy “adult beverages”, mostly wine and beer. I actually used to brew my own beer for awhile when I lived in Pittsburgh.

Blew up plenty of bottles trying to do that.

Career Focus: Pediatric Ophthalmology, Adult Strabismus, Pediatric Neuro-ophthalmology

Career: After completing my residency in Pittsburgh, I did two fellowships at the University of Iowa before joining the faculty at Vanderbilt University Medical Center. Currently I am Coleman Professor and Vice Chair for Clinical Affairs and Chief, Pediatric Ophthalmology Service at Vanderbilt Children’s Hospital, in Nashville.

Most important thing to you about having attended Pitt for Ophthalmology: At Pitt I received a very broad-based education. It really let me get a good handle on all different areas of ophthalmology and a really good background on those subspecialties. I didn’t feel like I left there lacking training in any one area. That has really helped me now in my career to recognize the needs in other areas than my own.

time the Residency Director was only part time with the Department, so there has been a lot of really good change over the years. I look forward to seeing continued great growth in the next few decades!

What made you stay involved with the Department of Ophthalmology and the Eye & Ear Foundation: I was really honored to be chosen as the inaugural Caputo lecturer when that series began. Brian was a very close friend of mine during my time in Pittsburgh. His loss was devastating so the honor of giving that first lecture and seeing his wife and several of our close friends when I was in town made that weekend a very special one for me.

Sean Donahue, MD, PhD

Recently, my connection with Pitt came full circle when I had the privilege of collaborating with Dr. Sahel and his team to implement a gene therapy for Leber Hereditary Optic Neuropathy that Dr. Sahel had developed. It was exciting for me to use advancements developed by people who are at my alma mater to help treat patients here in Nashville.

How has the campus/ department changed since your time at Pitt?

The Department is just so much bigger now and much better represented across various specialties. When I was a resident I believe we had one glaucoma specialist and two cornea specialists, one of whom was the chairman. I also can see how much more robust the training program for residents and fellows has become. At that

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We Want To Hear From You!

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ith the release of our new alumni newslet ter, Through the Looking Glass, we want to keep in touch with our alumni. Please share exciting personal or professional news with fellow alumni in future editions of our newsletter. Have you recently changed jobs? Got married? Published some exciting research? Welcomed a new member into your family? We want to know about it!

To update your contact information or to share personal and professional news, please visit http://ophthalmology.pitt. edu/alumni/alumni-verificationform

Webinar Information

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ecently, the Eye & Ear Foundation, in conjunction with the Departments of Otolaryngology and Ophthalmology at the University of Pittsburgh, launched a new bi-weekly webinar series entitled “Sight and Soundbites.” The webinars are presented by department faculty members and highlight their current research initiatives and treatment strategies. These webinars have proven to be an accessible and interactive way to stay connected with patients, donors, faculty, and alumni during the current COVID-19 shutdowns. If you would like to register to receive webinar invites, please visit www.eyeandear.org/webinars. To view past webinars, please click on the links below: •

How Far Can You Go: Brain Surgery Through the Nose

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The Myopia Story: Mr. Magoo Meets Harry Potter

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Robotic Surgery: Present Trends and Future Directions

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Visual Impairment and Visual Rehabilitation

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Exploring Novel Pathways To Provide Care To People In Need

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Imaging the Eye to Diagnose and Treat Macular Disorders

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Sleep and Dizziness: Are They Related?

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Understanding Diabetic Retinopathy

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Simulations in Tracheostomy Care

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Optic Nerve Regeneration

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Do you hear what I hear?

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The official registration and financial information of the Eye & Ear Foundation may be obtained from the Pennsylvania Department of State by calling toll free, within Pennsylvania, 1-800-732-0999.

Registration does not imply endorsement.

The Eye & Ear Foundation of Pittsburgh is a nonprofit 501 (C)(3) organization. Our mission is to support the research and academic efforts of the Departments of Ophthalmology and Otolaryngology at the University of Pittsburgh. Donations to support our research initiatives can be made online at eyeandear.org or by returning the enclosed envelope. For more information on the Foundation, our research, or the articles in this newsletter, please contact Katherine Troy, Director of Operations, at katherine@eyeandear.org or 412-864-1300.