About

Joshua L. Dunaief, MD, PhD, is the Adele Niessen Professor of Ophthalmology at the University of Pennsylvania's Perelman School of Medicine. He is a member of the Institute of Neuroscience, the Neuroscience Graduate Group, the Cell and Molecular Biology Graduate Group, and the Institute on Aging at the University of Pennsylvania. Dr. Dunaief serves as Chair of the D-COAP in the Department of Ophthalmology and is Vice Chair for Research at the Scheie Eye Institute. His research focuses on mechanisms and therapeutics for age-related retinal neurodegeneration, particularly age-related macular degeneration (AMD). His lab investigates the role of oxidative stress and iron overload in AMD pathogenesis, utilizing conditional knockout mouse models, human retinal tissue, and retinal cell culture to understand retinal iron homeostasis. His work has demonstrated that AMD retinas exhibit iron overload, which can cause oxidative damage, and that inflammation promotes cellular iron overload leading to cell death. His current efforts aim to develop treatments that protect the retina by targeting these mechanisms. Dr. Dunaief's educational background includes a B.A. in Biology from Harvard University, an M.D. and Ph.D. from Columbia University, and he is recognized for his contributions to understanding retinal neurodegeneration, with numerous publications in the field.

Research topics

• Immunology
• Medicine
• Bioinformatics
• Genetics
• Biology
• Neuroscience

Selected publications

• A Remarkable Tale: Increased Retinal Fluorescence Following Application of Permanent Marker Ink to Mouse Tails

  Investigative Ophthalmology & Visual Science · 2026-03-17

  articleOpen accessSenior authorCorresponding

  Purpose: Unusually high retinal fluorescence was observed during in vivo imaging among a few mice in our colony. Their tails had been marked with red Sharpie ink, a common practice for identification. They were observed licking the ink off their tails, suggesting possible oral intake of a fluorescent ink component that might accumulate in the retina. One component of red marker ink is the fluorophore Rhodamine 6G (R6G), suggesting that it might be responsible. Methods: We tested this hypothesis by tail marking C57Bl/6J mice with one line or four lines of red ink. Retinal fluorescence was monitored in vivo with confocal scanning laser ophthalmoscope (cSLO) imaging at baseline and from 6 hours to 2 weeks after marking. Retinas and brains were sectioned for histology. A second cohort of mice received an oral gavage of R6G at the concentration estimated in red ink, and retinal histology was performed. Results: Tail marking with red ink led to a transient, dose-dependent increase in retinal fluorescence in cSLO images, peaking at 6 hours. Histology revealed that this fluorescence was predominantly in the photoreceptor outer segments. This fluorescence localization was reproduced with oral R6G alone. Fluorescence in the brain was concentrated in the choroid plexus and ventricles. Conclusions: These results suggest that R6G can cross the gut-blood, blood-retina, and blood-cerebrospinal fluid barriers. This raises important technical considerations for experimental mouse identification and has potential applications for fluorescence imaging and central nervous system drug targeting.

  PublisherDOI

• Oral Deuterated Docosahexaenoic Acid Protects Against Onset and Progression of RPE Degeneration in a Mouse Model of Chronic Oxidative Stress

  Investigative Ophthalmology & Visual Science · 2026-04-14

  articleOpen accessSenior authorCorresponding

  Purpose: Oxidative stress is associated with many retinal diseases, including age-related macular degeneration (AMD). The purpose of this study is to investigate the efficacy of oral deuterated docosahexaenoic acid (D-DHA), an oxidation-resistant lipid, in a mouse model with features of dry AMD. We also evaluated whether long-term D-DHA dosing affects normal retinal structure or function. Methods: Liver-specific hepcidin (Hepc) and ceruloplasmin/hepcidin (Cp/Hepc) knock-out (KO) mice were fed experimental diet containing 0.25% D-DHA or control containing normal H-DHA during various stages of disease progression. Retinal pigment epithelium (RPE) damage was assessed with in vivo scanning laser ophthalmoscopy (SLO) imaging and histology. For the safety study, wild-type mice were fed the diets beginning in utero or at 3 months of age, continuing for 12 months. These mice were analyzed to assess retinal structure (SLO, optical coherence tomography [OCT], and transmission electron microscopy [TEM]), function (ERG), and gene expression (qPCR). Results: KO mice fed control diet developed expanding autofluorescent patches of hypertrophic RPE cells. This damage was markedly prevented or halted by diet with D-DHA, depending on age at diet onset. Wild-type mice administered diet with D-DHA from age 3 to 15 months had no retinal abnormalities. Mice administered D-DHA beginning in utero had normal retinal development and structure but minor deficits in ERG amplitudes and Rpe65 expression by age 12 months. Conclusions: Oral D-DHA was strongly protective against RPE ferroptosis, with minimal side effects. This study suggests that DHA oxidation is a key mechanism of retinal iron toxicity and supports the potential clinical application of D-DHA for diseases involving retinal oxidative stress.

  PublisherDOI

• Abstract 1334: FLASH proton radiotherapy mitigates corneal damage and stimulates wound healing in mice

  Cancer Research · 2025-04-21

  article

  Eye cancers are rare but highly aggressive, with significant risk to vision and quality of life. Worldwide, thousands are affected by ocular cancers, which are challenging to treat due to their proximity to sensitive structures. Proton radiotherapy (PRT) is the current gold standard for intraocular tumors due to its precision in limiting RT exposure to surrounding healthy tissue. However, the delicate location restricts the PRT dose that can be safely administered without risking damage to essential orbital structures. FLASH (FR), a novel approach delivering PRT at ultrahigh dose rates (>40 Gy/s) compared to standard dose rate PRT (SR, <0.003 Gy/s), has shown reduced toxicity in normal tissues like the brain and skin without compromising tumor control. However, its protective effects on eye structures remain unexplored. This study aims to investigate the potential of FR in preserving ocular tissues in a mouse model. Female C57BL/6J mice received 24 Gy of either FR or SR or remained untreated (control) using a "shoot-through" approach, in which both eyes received the same dose. Retinal and corneal damage were monitored using optical coherence tomography and confocal scanning laser ophthalmoscopy, with retinal vascular permeability evaluated by fluorescein angiography and retinal function by electroretinography (ERG). Corneal wound healing was assessed using corneal micro puncture. Evaluations occurred at one week, one, three, and five months post-PRT. Mice treated with SR showed significant corneal thickening and ulceration, leading to visual impairment, while those treated with FR did not. SR mice also showed declining ERG responses, suggesting diminished response to light stimuli, while FR mice demonstrated significantly less ERG abnormalities. Additionally, mice treated with SR showed over 55% reduction in eye surface area compared to both FR and control mice. Both SR and FR reduced retinal thickness, with no significant difference between the PRT treatment groups. Fluoresceine angiography showed no leakage in the retinal microvasculature. To further characterize corneal repair following PRT, we performed a corneal wound healing assay. Notably, FR demonstrated an enhanced wound healing response, with faster recovery of corneal incisions compared to both SR and control mice. This study presents a novel model for evaluating PRT-induced ocular damage, highlighting FR’s potential to protect healthy tissues. FR was particularly effective in preserving corneal integrity and promoting wound healing, which are crucial for maintaining both visual function and cosmetic outcomes. Ongoing studies aim to quantify the preservation of stem cells in the corneoscleral junction as a potential mechanism for the observed tissue-sparing effects. Citation Format: Elias El Hoyek, Uri Amit, Brent A. Bell, Vivian Lee, Joshua L. Dunaief, Costantinos Koumenis. FLASH proton radiotherapy mitigates corneal damage and stimulates wound healing in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1334.

  PublisherDOI

• Association of Age-Related Macular Degeneration with Cholelithiasis

  Ophthalmology Science · 2025-03-19 · 1 citations

  articleOpen access

  <h3>Purpose</h3> Dysregulated lipid metabolism likely contributes to the pathogenesis of age-related macular degeneration (AMD). There is an overlap in risk factors between AMD and diseases of lipid metabolism, such as cholelithiasis, suggesting that an association between these diseases could provide insight into AMD pathogenesis. This study sought to determine if there is an association between cholelithiasis and AMD. <h3>Design</h3> A cohort study was conducted using patients in the Optum deidentified Clinformatics Data Mart database from January 1, 2000, to June 30, 2022. <h3>Participants</h3> Patients over the age of 55 with ≥2 years of data and no prior history of AMD were included. The exposed cohort included patients who had a history of cholelithiasis, cholecystitis, or cholecystectomy. The control cohort included patients with gastroesophageal reflux disease (GERD), matched for age ±3 years, sex, race, and year of index date. <h3>Methods</h3> Propensity scores were created using multivariable logistic regression and applied to inverse probability of treatment weighting (IPTW). Cox proportional hazard regression modeling with IPTW was used to compare progression to AMD in each cohort. <h3>Main Outcome Measures</h3> Progression to AMD for patients with cholelithiasis, cholecystitis, or a history of cholecystectomy. <h3>Results</h3> A total of 332 536 patients with cholelithiasis and 776 591 matched GERD controls were analyzed. After IPTW, the mean age (±standard deviation) was 66.6 ± 9.4 years in the cholelithiasis cohort and 67.5 (±10.3) years in the GERD cohort. Women comprised 58% of the cholelithiasis cohort and 57% of the GERD cohort. In the cholelithiasis cohort, 3511.7 (1.14%) were diagnosed with AMD, compared with 23 367.1 (2.92%) in the GERD cohort and corresponding to a significantly decreased hazard of AMD (adjusted hazard ratio [aHR] = 0.72, 95% confidence interval [CI]: 0.69–0.75, <i>P</i> < 0.0001). In the subanalysis, before IPTW weighting, AMD developed in 3809 of 275 897 (1.4%) patients with only cholelithiasis (aHR = 0.76, 95% CI: 0.73–0.80, <i>P</i> < 0.0001), 335 of 47 166 (0.71%) patients with cholecystitis (aHR = 0.54, 95% CI: 0.47–0.61, <i>P</i> < 0.0001), and 114 of 9473 (1.20%) patients who underwent cholecystectomy (aHR = 0.50, 95% CI: 0.41–0.63, <i>P</i> < 0.0001). <h3>Conclusions</h3> Cholelithiasis was associated with a 28% hazard reduction in AMD. More severe gallbladder disease conferred greater protection. <h3>Financial Disclosure(s)</h3> Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  PublisherOA PDFDOI

• Loss of monocyte chemoattractant protein-1 reduced monocyte recruitment and preserved retinal ganglion cells in a mouse model of hypertensive glaucoma

  Experimental Eye Research · 2025-03-07 · 5 citations

  articleOpen access
  PublisherOA PDFDOI

• FLASH PROTON RADIATION REDUCES OCULAR TOXICITY AND PRESERVES VISION BY MINIMIZING CORNEAL CELL DEATH IN A PRECLINICAL MODEL

  Radiotherapy and Oncology · 2025-09-01

  article
  PublisherDOI

• Oral Ursodeoxycholic Acid Is Associated With Decreased Rate of AMD

  Clinical Therapeutics · 2025-09-08 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Tamoxifen protects photoreceptors in the sodium iodate model

  Experimental Eye Research · 2024-04-01 · 5 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Testosterone promotes photoreceptor degeneration in the sodium iodate model

  Experimental Eye Research · 2024-12-20 · 1 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Reversing Severe Chronic Kidney Disease Before and After COVID-19 Infection With a Whole-Food, Plant-Based, Low Inflammatory Foods Everyday (LIFE) Diet

  Current Developments in Nutrition · 2024-06-29

  articleOpen access

  Objectives: To determine the impact of the a micronutrientrich, whole food plant-based Low Inflammatory Foods Everyday (LIFE) diet on a 66 year old male with stage 4 chronic kidney disease (CKD) secondary to uncontrolled Type II Diabetes Mellitus.Methods: The patient was counseled to adopt the LIFE diet.Objective laboratory measurements, including GFR, creatinine, HbA1c, BUN, albumin to creatinine ratio in urine, hsCRP, and beta carotene, were obtained at baseline and repeatedly over the course of the intervention.Results: Within three months, his GFR increased by 88% to 49 mL/min, creatinine decreased by 40% to 1.66 mg/dL, and beta-carotene increased by 794% to 143 mcg/dL.Soon afterward, the patient discontinued the diet for one month and was then hospitalized with COVID-19.After the infection, he remained inconsistent with the LIFE diet; his GFR was reduced to 34 mL/min, creatinine increased to 2.2 mg/dL, and beta-carotene decreased to 89 mcg/dL.The patient once again became adherent to the LIFE diet, and his kidney function rebounded within three months.Conclusions: In this case study, we demonstrate that consumption of the LIFE Diet resulted in improvements in GFR and creatinine in a patient with severe stage 4 CKD, while increasing the serum levels of beta-carotene.This is the first case study to demonstrate the potential reversal of stage 4 CKD with either dietary or medication interventions.This report indicates that a micronutrient-rich, whole food plant-based diet may improve kidney function in patients with severe CKD.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21EY018922

  NIH · $445k · 2010

• The IL-6 Induced Retinal Iron Sequestration Response

  NIH · $2.4M · 2019–2024

• NIH Grant K08EY000417

  NIH · $861k · 2005

• Retinal Iron Health in Transport and Disease

  NIH · $9.8M · 2004–2028

• PENN Vision Clinical Scientist Program

  NIH · $11.1M · 2004–2026

Frequent coauthors

• Ying Song

  University of Pennsylvania

  206 shared

• Delu Song

  University of California, San Diego

  143 shared

• Gui‐Shuang Ying

  University of Pennsylvania

  79 shared

• Tzvete Dentchev

  University of Pennsylvania

  79 shared

• Majda Hadziahmetovic

  Duke University

  74 shared

• Jared Iacovelli

  Moderna Therapeutics (United States)

  69 shared

• Yafeng Li

  New York Eye and Ear Infirmary

  65 shared

• Paul Hahn

  University of Kassel

  65 shared

Labs

• Dunaief LabPI

Awards & honors

• Adele Niessen Professor of Ophthalmology
• Member, Institute of Neuroscience, University of Pennsylvani…
• Member, Neuroscience Graduate Group, University of Pennsylva…
• Member, Institute on Aging, University of Pennsylvania
• Member, Cell and Molecular Biology Graduate Group, Universit…