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Updated: May 2, 2026
Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
Published on: July 6, 2022
Spatial proteomics of Onchocerca volvulus with pleomorphic neoplasms shows local and systemic dysregulation of
Lucia S Di Maggio1, Kerstin Fischer1, Bruce A Rosa1
1Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
Onchocerca volvulus is the agent of onchocerciasis (river blindness) and targeted by WHO for elimination though mass drug administration with ivermectin. A small percentage of adult worms develop pleomorphic neoplasms (PN) that are positively associated with the frequency of ivermectin treatment. Worms with PN have a lower life expectancy and a better understanding about the proteins expressed in PN, and how PN affect protein expression in different tissues could help to elucidate the mechanisms of macrofilaricidal activity of ivermectin. Within a clinical trial of drug combinations that included ivermectin, we detected 24 (5.6%) O. volvulus females with PN by histology of paraffin embedded nodules. To assess the protein inventory of the neoplasms and to identify proteins that may be associated with tumor development, we used laser capture microdissection and highly sensitive mass spectrometry analysis. Neoplasm tissue from three female worms was analyzed, and compared to normal tissues from the body wall, uterus and intestine from the same worms, and to tissues from three females without PN. The healthy females showed all intact embryogenesis. In PN worms, 151 proteins were detected in the body wall, 215 proteins in the intestine, 47 proteins in the uterus and 1,577 proteins in the neoplasms. Only the uterus of one PN female with some stretched intrauterine microfilariae had an elevated number of proteins (601) detectable, while in the uteri of the healthy females 1,710 proteins were detected. Even in tissues that were not directly affected by PN (intestine, body wall), fewer proteins were detected compared to the corresponding tissue of the healthy controls. Immunolocalization of the calcium binding protein OvDig-1 (OVOC8391) confirmed the detection in PN by mass spectrometry. In conclusion we identified proteins that are potentially linked to the development of PN, and systemic dysregulation of protein expression may contribute to worm mortality.
Insights
Mass drug administration with ivermectin targets river blindness (onchocerciasis). This study identified proteins in neoplasms (PN) of the parasite Onchocerca volvulus, potentially explaining ivermectin
Area of Science:
- Parasitology
- Molecular Biology
- Drug Discovery
Background:
- Onchocerca volvulus causes river blindness, targeted for elimination via ivermectin.
- A subset of worms develops pleomorphic neoplasms (PN), linked to ivermectin treatment frequency.
- Understanding PN protein expression may reveal ivermectin's macrofilaricidal mechanisms.
Purpose of the Study:
- To identify proteins within PN and associated with their development.
- To compare protein expression in PN tissues versus normal tissues.
- To investigate systemic protein dysregulation in ivermectin-treated worms.
Main Methods:
- Histological detection of PN in O. volvulus females from a clinical trial.
- Laser capture microdissection of neoplasm and normal tissues.
- High-sensitivity mass spectrometry for protein identification and quantification.
Main Results:
- 1,577 proteins identified in PN; significantly fewer proteins detected in other tissues of PN-affected worms compared to controls.
- Uterus of one PN worm showed altered protein count (601) versus healthy controls (1,710).
- Calcium-binding protein OvDig-1 confirmed in PN via immunolocalization.
Conclusions:
- Proteins potentially linked to PN development were identified.
- Systemic dysregulation of protein expression may contribute to worm mortality.
- Findings offer insights into ivermectin's effects on O. volvulus.
