Ula V. Jurkunas, M.D.

Harvard Medical School

Associate Professor of Ophthalmology
Co-Director, Cornea Center of Excellence

Massachusetts Eye and Ear

Department of Ophthalmology Scholar

Schepens Eye Research Institute of Massachusetts Eye and Ear

Associate Scientist

Research Summary

Center/Research Area Affiliations

Biography

Dr. Jurkunas performs corneal and refractive surgery at Mass. Eye and Ear. Her two main research areas include the pathogenesis of Fuchs’ endothelial corneal dystrophy (FECD)—with emphasis on the role of oxidative stress in endothelial cell death—and the development of cultivated epithelial (stem) cell transplantation for the treatment of limbal stem cell deficiency.

In addition, she teaches residents and fellows about corneal surgical procedures and the diagnosis and clinical management of corneal and refractive conditions. Her main clinical areas of expertise are corneal endothelial dysfunction, femtosecond cataract surgery, refractive surgery, and lamellar keratoplasty, including DMEK and complex DSAEK.

Education

M.D., Cum Laude, University of Louisville (2000)

Postgraduate Training

Residency, Boston University (2004)
Fellowship, Mass. Eye and Ear (2004-2006)
Fellowship, Kyoto Prefectural University of Medicine (2006)

Honors

2017: ARVO Foundation/Pfizer Ophthalmics Carl Camras Translational Research Award
2016: American Academy of Ophthalmology Achievement Award
2013: Young Investigator Award, Alcon Research Institute
2010: Ophthalmology Scholar, Harvard Ophthalmology
2008: Norman Knight Leadership Development Award, Mass. Eye and Ear
2008: ISER Travel Fellowship, Beijing, China
2008: Ophthalmology Awardee of the Friends of Mass. Eye and Ear Award
2008: ARVO/Alcon Early Career Clinician-Scientist Research Award
2007: Best Scientific Abstract Award, the 25th Biennial Cornea Research Conference, Mass. Eye and Ear
2004: Best Scientific Poster Award, New England Ophthalmological Society, “Novel Role of Keratocytes in Corneal Edema”

Her Story

Clinical Care

Dr. Jurkunas is a clinician scientist who performs corneal and refractive surgery at Massachusetts Eye and Ear and Mass General Hospital.

Research

A globally recognized scientist, author, and lecturer, Dr. Jurkunas' work has led to numerous peer-reviewed publications, review articles, and presentations nationally and internationally. Her research is focused on two main areas:

  1. The pathogenesis of Fuchs endothelial corneal dystrophy with emphasis on the role of oxidative stress in endothelial cell death seen in Fuchs
  2. The development of autologous cultivated epithelial stem cell constructs for patients with corneal blindness due to limbal stem cell deficiency

Pathogenesis of Fuchs' Endothelial Dystrophy

Dr. Jurkunas conducts award-winning research on the pathophysiology of Fuchs' endothelial corneal dystrophy (FECD). She has pioneered the efforts that linked oxidative stress with the pathogenesis of Fuchs' dystrophy. Today, she heads a fully staffed and NIH-funded (R01) laboratory that studies the mechanisms involved in the corneal endothelial degeneration seen in FECD. Her studies focus on the role of oxidative stress in cell-extracellular matrix interactions, estrogen metabolism, DNA damage and repair, and mitochondrial biogenesis in FECD. The Jurkunas laboratory was the first to derive a telomerase-immortalized corneal endothelial cell line that provides an important new tool for the in vitro study of corneal endothelial cell biology. Moreover, she has developed Fuchs' endothelial cell lines and animal models aimed at determining the link between how genetics and oxidative stress cause molecular and cellular damage in the susceptible FECD endothelium. These studies are significant because understanding the key regulators of antioxidant defense and oxidative stress-induced cellular damage may facilitate development of pharmacotherapeutic treatment for FECD patients.

Dr. Jurkunas was among the first Harvard Ophthalmology faculty members to be selected for the prestigious K12 Harvard Vision Clinical Scientist Development Program, which is funded by the National Institutes of Health/National Eye Institute (NIH/NEI).

Since then, Dr Jurkunas has received RO1 funding from NEI/NIH for her research, and she has filed an international patent application for the treatment of corneal endothelial disorders.

Stem Cells for Limbal Cell Deficiency

In collaboration with the Center for Human Cell Therapy Boston, Dr. Jurkunas is pioneering the development of cultured autologous limbal epithelial stem cell constructs (CALEC) to treat patients with corneal blindness resulting from limbal stem cell deficiency. She was awarded a Production Assistance for Cellular Therapies (PACT) grant from the National Heart/Lung and Blood Institute of the NIH, which laid groundwork for the study of stem cell biology for the regeneration of corneal epithelium. The latter studies have led to the translational development of stem cell therapy in corneal disorders. Dr. Jurkunas's Investigational New Drug (IND) was approved by the FDA, and she is performing a Phase I/II study using stem cells to treat corneal blindness. Recently, she received funding for a UG1 grant from the NIH/NEI to perform the first-in-human study using cultivated autologous limbal epithelial cells (CALEC) transplantation at Mass. Eye and Ear, in collaboration with Cell Manufacturing Facility at Dana-Farber Cancer Institute. The development of the methodology to transplant CALEC cells created from the patient’s own tissue holds great promise in the area of regenerative medicine and offers hope for a significant number of patients worldwide.

Teaching

Dr. Jurkunas also instructs residents and fellows in corneal, cataract, and refractive surgery, as well as in the clinical management and diagnosis of corneal and refractive conditions.

Projects

Research Interests

  • Pathogenesis of Fuchs’ endothelial corneal dystrophy
  • Oxidative stress and aging of the endothelium
  • Ocular surface reconstruction with stem cells
  • Corneal transplantation (e.g., DMEK and DSAEK)

Fuchs’ Endothelial Corneal Dystrophy (FECD)

Dr. Jurkunas aims to identify the cause of FECD, which is a female-predominant, age-related disease. It is among the most common causes of blindness from corneal swelling, and a second-most common cause of corneal transplants in the United States. Because little is known about what triggers corneal endothelial cells to die in FECD, there is no effective treatment, and corneal transplantation is the only currently available measure to restore lost vision.

Over past several years, Dr. Jurkunas has developed techniques to analyze differences in protein composition between normal and FECD corneal endothelial cells. The most striking findings were the discovery of an intricate protein system in normal endothelium that regulates cellular ability to respond to oxidative stress and regulates cell-to-cell interactions. Altered amounts of these crucial proteins were noted in FECD cells, implicating a potential cellular mechanism of the disease. Such insights into the mechanism of what triggers corneal endothelium to die will lead to the development of preventive and therapeutic approaches to this common blinding condition.

Dr. Jurkunas was recently awarded a $2.5 million grant from the National Eye Institute of the NIH to study: “The Role of oxidative stress in the pathogenesis of Fuchs' endothelial corneal dystrophy.” The research proposal specifically seeks to understand why there is greater female prevalence of FECD by studying reactive estrogen metabolites, mitochondrial biogenesis, and DNA damage response pathways in the disease. Dr. Jurkunas will collaborate with the Wiggs and Vandenberghe laboratories in order to understand how the underlying genetic causes of FECD lead to the mitochondrial dysfunction and cell death. These studies are significant, as they have great potential to lead to the development of novel cytoprotective and anti-aging therapies for FECD patients.

  • 2010-2015: Role of oxidative stress in pathogenesis of Fuchs' endothelial corneal dystrophy. The major goal of the study is to determine specific cellular mechanisms that can be manipulated to reverse endothelial cell degeneration due to oxidative stress.
  • 2008-present: Cellular changes in Fuchs' ndothelial Cocrneal dystrophy: An in vivo confocal microscopy study. The major goal of the study is to assess the involvement of corneal nerves and cellular changes in patients with Fuchs dystrophy.
  • 2009-present: Utilization of confocal microscopy for the assessment of corneal nerve and cellular characteristics in corneal dystrophies. The goal of this study is to investigate density and morphology of corneal cells in corneal dystrophies using in-vivo confocal microscopy.
  • 2012-present: Regional variability in endothelial cell density in Fuchs' endothelial corneal dystrophy: A retrospective study. The goal of this study is to compare endothelial cell density using specular and confocal microscopies and to analyze regional variability of ECD between guttate and non-guttate areas of patients with FECD.

Corneal Stem Cell Deficiency

Dr. Jurkunas’ second main area of research is the development of alternative corneal transplantation techniques for patients with damaged corneal stem cells. Corneal epithelial stem cells are located in the periphery of the cornea and are very susceptible to multiple infections and inflammatory disorders. The attempts to treat the ocular surface with a standard corneal transplant in these patients have been unsuccessful due to immunologic rejection and subsequent graft failure.

Dr. Jurkunas is investigating the alternative sources of corneal epithelium, one of which is oral mucosa. She has  successfully harvested mouth cells and is now planning to apply this technique to patient care. The development of the methodology of cultivated oral mucosal epithelial transplantation demonstrates great promise in the area of regenerative medicine and offers hope for many patients with vision loss worldwide.

  • 2009-present: Safety and efficacy of bevacizumab in high-risk corneal transplant survival. The goal of the study is to determine the safety and efficacy of subconjunctival and topical bevacizumab treatment in patients who have undergone high-risk corneal transplantations.
  • 2010-present: In vivo confocal microscopy in corneal graft rejection. The goal of this study is to investigate early detection of prognosticators for corneal graft rejection by detecting cellular changes after corneal transplantation by using in-vivo confocal microscopy.
  • 2011-present: Relative efficacy of loteprednol (Lotemax®) vs. loteprednol/tobramycin (Zylet®) in treatment of chronic ocular surface inflammation associated with Meibomian gland dysfunction (MGD)/posterior blepharitis. The goal of the study is to determine whether Zylet (a corticosteroid and antibiotic) is superior to Lotemax (steroid only) in managing meibomian gland dysfunction associated ocular surface disease.

Current Research Funding

2015-2020
NEI/NIH R01 EY020581: Principal Investigator
Role of oxidative stress in pathogenesis of Fuchs' endothelial corneal dystrophy
$1,375,328

Publications

Selected Publications

Dr. Jurkunas has published more than 40 peer-reviewed articles. Below is a list of selected publications. View her publications on PubMed.

  1. Homer N, Jurkunas UV. The use of femtosecond laser in refractive and cataract surgery. Int Ophthalmol Clin. 2017 Fall;57(4):1-10.
  2. Syed ZA, Tran JA, Jurkunas UV. Peripheral endothelial cell count Is a predictor of disease severity in advanced Fuchs endothelial corneal dystrophy. Cornea. 2017 Oct;36(10):1166-1171 
  3. Gupta R, Kinderyte R, Jacobs DS, Jurkunas UV. Elimination of anterior corneal steepening With Descemet membrane endothelial keratoplasty in a patient with Fuchs dystrophy and keratoconus: implications for IOL calculation. Cornea. 2017 Oct;36(10):1260-1262.
  4. Benischke AS, Vasanth S, Miyai T, Katikireddy KR, White T, Chen Y, Halilovic A, Price M, Price F Jr, Liton PB, Jurkunas UV. Activation of mitophagy leads to decline in Mfn2 and loss of mitochondrial mass in Fuchs endothelial corneal dystrophy. Sci Rep. 2017 Jul 27;7(1):6656.
  5. Richarme G1, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science. 2017 Jul 14;357(6347):208-211.

 

 

Laboratory

Current Members of Dr. Ula Jurkunas’ Laboratory

Research Assistant II
Neha Deshpande, M.S.

Research Associate
Cailing Liu, Ph.D.

Research Fellow
Taiga Miyajima, M.D.

Investigator
Shivakumar Vasanth, Ph.D.

Postdoctoral Fellow
Tomas White, Ph.D.

Alumni

More than 20 trainees have worked in Dr. Jurkunas’ laboratory.