Translational Immunoimaging and Neuroimaging Demonstrate Corneal Neuroimmune Crosstalk
Pedram Hamrah1, Yashar Seyed-Razavi, Takefumi Yamaguchi
1*Center of Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA; †Boston Image Reading Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA; and ‡Cornea Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA; Programs in §Immunology; and ¶Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA; and ‖Department of Ophthalmology, Ichikawa General Hospital, Tokyo Dental College, Chiba, Japan.
Insights
Corneal imaging reveals that increased dendritiform immune cells (DCs) correlate with ocular inflammation and reduced corneal nerve density. This finding highlights DCs as a potential biomarker for inflammatory eye diseases and therapeutic monitoring.
Area of Science:
- Ophthalmology
- Immunology
- Neuroscience
Background:
- Corneal immunoimaging and neuroimaging enable in vivo analysis of immune cells and nerves, revealing alterations beyond clinical examination.
- Translational research bridges basic science and clinical practice in ocular immunology.
- Dendritiform immune cells (DCs) have been identified in the central murine cornea.
Purpose of the Study:
- To review recent translational research in corneal immunoimaging and neuroimaging.
- To explore the utility of DCs as a biomarker for inflammatory ocular surface diseases.
- To investigate the relationship between corneal nerves and immune regulation.
Main Methods:
- Laser in vivo confocal microscopy (IVCM) for visualizing corneal immune cells and nerves.
- Analysis of DC density, size, and correlation with clinical signs, symptoms, and tear cytokines.
- Preclinical research on inflammatory states in denervated corneas.
Main Results:
- IVCM allows visualization of DCs in patients, demonstrating their potential as a biomarker.
- Increased DC density and size were observed in ocular disease, correlating with disease severity and inflammation.
- A negative correlation between DC density and subbasal nerve density was found.
- Corneal nerves appear to play a role in regulating corneal homeostasis and immune privilege.
Conclusions:
- DCs are a promising surrogate biomarker for inflammatory ocular surface diseases, useful for monitoring treatment efficacy and as a clinical trial endpoint.
- Corneal nerves are implicated in the regulation of corneal immune privilege and homeostasis.
- IVCM is a valuable tool for in vivo corneal research and clinical assessment.
Abstract:
Corneal immunoimaging and neuroimaging approaches facilitate in vivo analyses of the cornea, including high-resolution imaging of corneal immune cells and nerves. This approach facilitates the analyses of underlying immune and nerve alterations not detected by clinical slit-lamp examination alone. In this review, we describe recent work performed in our translational ocular immunology center with a focus on "bench-to-bedside" and "bedside-to-bench" research. The ability to visualize dendritiform immune cells (DCs) in patients with laser in vivo confocal microscopy (IVCM), recently discovered in the central murine cornea, has allowed us to demonstrate their utility as a potential surrogate biomarker for inflammatory ocular surface diseases. This biomarker for inflammation allows the measurement of therapeutic efficacy of anti-inflammatory drugs and its utility as an endpoint in clinical trials with high interobserver agreement. IVCM image analyses from our studies has demonstrated a significant increase in DC density and size in ocular disease, a positive correlation between DC density and clinical signs and symptoms of disease and pro-inflammatory tear cytokines, and a strong negative correlation between DC density and subbasal nerve density. In conjunction with preclinical research investigating the inflammatory state in a partial or fully denervated cornea, our results indicated that corneal nerves are directly involved in the regulation of homeostasis and immune privilege in the cornea.
