About

Dr. Dong Feng Chen is an Associate Professor of Ophthalmology at the Schepens Eye Research Institute. His research focuses on the underlying causes of neurodegeneration and the development of neural enhancement and regenerative therapies for treating degenerative diseases of the eye and brain, with the goal of reversing blindness. Using mouse genetic tools, his laboratory was the first to demonstrate the full-length regeneration of the optic nerve from the eye into the brain in early postnatal mice. His work has led to discoveries showing that neural stem cells, which can give rise to neurons and glia, are widely distributed in the adult brain and retina but are kept quiescent by inhibitory niche signals. His research has identified pathways that regulate neuroregeneration and repair in the adult central nervous system, suggesting the possibility of restoring function and reversing blindness by reactivating endogenous regenerative potential. Recent studies in his lab have also uncovered an unexpected link among neuron loss, microflora, and immune responses in glaucoma, pioneering immunotherapy approaches for neurodegenerative diseases of the eye.

Research topics

• Biology
• Neuroscience
• Medicine
• Pathology
• Surgery
• Immunology
• Ophthalmology
• Chemistry
• Traditional medicine
• Pharmacology
• Internal medicine

Selected publications

• Mitochondria transplantation preserves retinal ganglion cells and promotes CNS axonal regeneration

  Free Radical Biology and Medicine · 2026-04-06

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Direct Conversion of Mouse Fibroblasts into Photoreceptor-like Cells

  Cells · 2026-02-09

  articleOpen access

  The purpose of our study is to explore the potential of a transcription factor-based strategy for directly converting mouse fibroblasts into photoreceptor-like cells. The mouse cDNAs of Ascl, Crx, Ngn1, Nrl, and Otx2 were cloned into a modified commercial adenoviral vector. Mouse embryonic fibroblasts (MEFs) were isolated from E13.5 embryos, and mouse postnatal fibroblasts (MPFs) were isolated from three-day-old mice. A pool of adenoviruses containing five genes was prepared to infect MEFs or MPFs once daily for two days. The MEFs or MPFs were incubated in a specific medium supplemented with forskolin and were changed every two days. After 7 or 14 days, the photoreceptor-like cells were assayed via immunofluorescence or polymerase chain reaction with reverse transcription (RT–PCR). The photoreceptor-like cells were then transplanted into adult C57BL/6 mouse retinas and were assessed by immunofluorescence 14 days following transplantation. Screening from a pool of five candidate genes, we reported that a combination of only three factors—Crx, Nrl, and Otx2—was sufficient to convert mouse embryonic and postnatal fibroblasts into photoreceptor-like cells. The induced photoreceptor-like cells expressed photoreceptor-specific proteins such as Recoverin, Rhodopsin, and Opsin and integrated into the outer nuclear layer of the retina following transplantation. This exploratory study provides preliminary evidence that fibroblasts can be directly converted into photoreceptor-like cells, suggesting a cellular model and potential source for future transplantation strategies aimed at retinal repair.

  PublisherOA PDFDOI

• Non-invasive bioelectrical therapy suppresses retinal neovascularization by modulating cellular metabolism and inflammation

  Cell Communication and Signaling · 2025-11-06 · 1 citations

  articleOpen accessSenior author

  BACKGROUND: Pathological retinal neovascularization, a major cause of blindness, occurs in conditions such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Microglial activation and chronic neuroinflammation play critical roles in disease progression by promoting vascular permeability and angiogenesis. While anti-VEGF therapies are the current standard of care, their efficacy is limited, requiring frequent intraocular injections and raising concerns about long-term retinal health. Noninvasive transpalpebral electrical stimulation (TpES) has emerged as a potential alternative therapy, but its mechanism and therapeutic impact remain poorly understood. METHODS: To investigate the therapeutic effects of TpES, we applied daily microcurrent stimulation (300 µA, 20 Hz, 4 min) in laser-induced choroidal neovascularization (CNV) and streptozotocin (STZ)-induced DR mouse models. Vascular pathology was assessed using fluorescein angiography, optical coherence tomography (OCT), and immunohistochemistry. Mechanistic studies were conducted using primary microglia and human retinal endothelial cells (HREC) to evaluate TpES-induced changes in intracellular calcium ([Ca²⁺]i) signaling, mitochondrial membrane potential, and ATP production. Additionally, human RPE/choroidal explants from healthy, AMD, and DR donors were cultured to assess TpES effects on angiogenesis in healthy and pathological human tissues. RESULTS: TpES significantly reduced vascular leakage (by ~ 30%, p < 0.001) and lesion size in the CNV model (p < 0.05), while also suppressing microglial infiltration and VEGF-A expression. In the DR model, TpES attenuated microaneurysm formation, preserved endothelial tight junctions (in vitro). Mechanistic studies revealed that TpES suppressed ATP-induced microglial activation by reducing mitochondrial membrane potential and intracellular ATP levels, leading to depletion of ER calcium stores and inhibition of proinflammatory and proangiogenic signaling. TpES also directly suppressed endothelial cell migration and tube formation, as well as angiogenic sprouting in human RPE/choroidal explants. CONCLUSIONS: These findings establish TpES as a dual-action therapy that mitigates both inflammation and pathological angiogenesis by modulating microglial and endothelial metabolism. Given its noninvasive nature and ability to target key pathways in retinal pathology, TpES represents a promising therapeutic strategy for AMD, DR, and other retinal vascular diseases.

  PublisherOA PDFDOI

• Assessment of Visual Function in Mice Using Light/Dark Box and Multi-Feature Machine Learning

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-10

  preprintOpen accessCorresponding

  Abstract The light/dark box test can be used to assess visual function in rodents based on their spontaneous behavior in response to light. Commonly used assay relies on a single behavioral metric, dwell time in the light or dark compartment, which may be influenced by factors other than vision, leading to unreliable assessment results. To overcome this, we developed a multi-feature machine learning paradigm by extracting multiple mouse behavioral metrics, standardizing them as features to train machine learning models, thereby achieving reliable and automated vision assessment. We systematically compared the classification performance of single-metric versus multi-feature machine learning approaches in sighted and blind mice, using wild-type and rhodopsin-deficient mice, with a subset further subjected to double optic nerve crush. We found that the multi-feature method can improve classification performance and exhibit great robustness to different experimental settings. Additionally, we further improved model performance by applying feature importance analysis and constructing an optimized feature subset. These findings suggest that the reliability of commonly used single dwell time measure for vision assessment could become unreliable, as shown in our experiment, probably because in addition to vision other factors also impact dwell time. Our study demonstrated an improved assessment method based on a combination of multiple behavior features through machine learning. Author Summary Assessing visual function in mice is essential for studying eye diseases and drug development. The light/dark box test evaluates visual function by measuring the spontaneous behavioral response of mice to light, providing a training-free behavioral approach that helps simplify the assessment process and improve research efficiency. However, traditional light/dark box tests rely on a single behavioral metric, dwell time in the light or dark compartment, to assess visual function, which may be influenced by factors other than vision, such as anxiety and exploratory behavior, leading to limited reliability of assessment results. Here, we demonstrate that integrating multiple behavioral features through machine learning can improve the reliability and stability of vision assessment. By automatically tracking and analyzing various behavioral metrics of mice, such as movement patterns, speed, and spatial preferences, the proposed method can more reliably distinguish between sighted and blind mice. Furthermore, the method demonstrates stable performance across different experimental settings, showing good applicability. This automated, reliable, and easily generalizable method can provide a convenient and efficient means for visual assessment in preclinical research, facilitating vision disease research and drug development.

  PublisherOA PDFDOI

• Mitochondria Transplantation Preserves Retinal Ganglion Cells and Promotes CNS Axonal

  SSRN Electronic Journal · 2025-01-01 · 1 citations

  preprintOpen accessSenior author
  PublisherDOI

• DNA Methylation Dynamics in a Mouse Model of Retinitis Pigmentosa

  American Journal Of Pathology · 2025-06-24

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

  Neural Regeneration Research · 2024-01-08 · 6 citations

  articleOpen accessSenior author

  JOURNAL/nrgr/04.03/01300535-202419110-00034/figure1/v/2024-03-08T184507Z/r/image-tiff Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors, leading to progressive photoreceptor loss. Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival. This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation (tcES) in mice affected by inherited retinal degeneration. Additionally, the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans. In this study, we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular, sine, and ramp waveforms. To investigate the functional effects of electrical stimulation on photoreceptors, we used human retinal explant cultures and rhodopsin knockout (Rho-/-) mice, demonstrating progressive photoreceptor degeneration with age. Human retinal explants isolated from the donors' eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro. Photoreceptor density was evaluated by rhodopsin immunolabeling. In vivo Rho-/- mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms. Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response (OMR), respectively. Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas. Oscilloscope recordings indicated effective delivery of rectangular, sine, and ramp waveforms to the retina by transcorneal electrical stimulation, of which the ramp waveform required the lowest voltage. Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes. The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro (~0.5-1.5°C). Electrical stimulation increased photoreceptor survival in human retinal explant cultures, particularly at the ramp waveform. Transcorneal electrical stimulation (rectangular + ramp) waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results. Histology and immunolabeling demonstrated increased photoreceptor survival, improved outer nuclear layer thickness, and increased bipolar cell sprouting in Rho-/- mice. These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina, improves photoreceptor survival in both human and mouse retinas, and increases visual function in Rho-/- mice. Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

  PublisherDOI

• Testing Visual Function by Assessment of the Optomotor Reflex in Glaucoma

  Methods in molecular biology · 2024-10-21 · 2 citations

  article
  PublisherDOI

• Growing microglia in the lab

  eLife · 2024-10-28

  articleOpen accessSenior author

  Transplanting microglia derived from human stem cells into mice reveals new possibilities for treating neurodegenerative eye diseases.

  PublisherDOI

• Bioengineering strategy to promote CNS nerve growth and regeneration via chronic glutamate signaling

  Acta Biomaterialia · 2024-10-18 · 5 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01EY017641

  NIH · $1.5M · 2011

• Core Grant for Vision Research

  NIH · $17.7M · 1997–2027

• NIH Grant R01EY012983

  NIH · $2.0M · 2006

• NIH Grant R21DA024803

  NIH · $529k · 2011

• The Molecular Basis Underlying Optic Nerve Growth in Development and Regeneration

  NIH · $3.2M · 2016–2022

Frequent coauthors

• Kin‐Sang Cho

  Smith-Kettlewell Eye Research Institute

  572 shared

• Tor Paaske Utheim

  OsloMet – Oslo Metropolitan University

  162 shared

• Karen L. Chang

  National Taiwan University

  148 shared

• Chenying Guo

  Boston Biomedical Research Institute

  99 shared

• Li Pan

  Hebei University

  90 shared

• Anton Lennikov

  Smith-Kettlewell Eye Research Institute

  84 shared

• Huihui Chen

  Zhongda Hospital Southeast University

  81 shared

• Ajay Ashok

  Massachusetts Eye and Ear Infirmary

  77 shared