Ocular Microbiology and Immunology Group
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2024 OMIG Abstract

Cell and Mouse Model Systems for Investigating Ocular Mpox and Antiviral Therapeutics

Sankara Naynar Palani¹, Sneha Singh², Anne Zaiss¹, Arjit Vijey Jeyachandran¹, Zeeshan Ahmad²,
Ashok Kumar², Vaithi Arumugaswami<sup>1

1</sup>Department of Pharmacology, University of California Los Angeles, Los Angeles, CA;
²Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI

Purpose: Monkeypox (Mpox) virus (MPXV) is a zoonotic pathogen that spreads rapidly through human-human transmission via respiratory droplets and direct contact, causing painful pock lesions and systemic ailments. MPXV infection is also associated with various mild to severe ophthalmic conditions collectively termed, "ocular mpox," including vision-threatening conditions like corneal scars and keratitis. The 2022 MPXV strain caused near 100,000 infections and 115 deaths globally, showing increased spread compared to previous strains. The pathogenic process of ocular mpox is poorly understood. Besides, there is no well-defined treatment options available for ocular Mpox. Therefore, we set out to develop human cell and mouse model systems to understand ocular cell injury mechanisms and to assess antiviral drugs.

Methods: We evaluated the susceptibility of human primary corneal cells to Mpox virus infection. We also tested the effectiveness of currently approved smallpox antiviral drug Tecovirimat (TPOXX) and screened a host-targeted antiviral drug compound library against MPXV. Furthermore, we investigated the susceptibility of various mouse strains upon corneal and periocular viral inoculation to establish in vivo ocular disease model.

Results: We have observed that the MPXV strains readily infected primary corneal cells and caused cell death as well as inflammatory responses. The 2022 MPXV (Clade IIb) was less susceptible to TPOXX treatment in the corneal cell culture compared to the Clade IIa 2003 MPXV. An antiviral drug screen using 3500 compounds comprised of kinase inhibitors and metabolites yielded 138 hits that prevented ocular epithelial cell death. Furthermore, corneal, and periocular inoculation of 2022 MPXV strain in wild type and immunocompromised mice strains resulted in development of pock-lesions on the eyelids, ptosis and keratitis.

Conclusions: We have developed ocular cell culture and animal models to investigate host and viral factors contributing to ocular mpox and to discover potential novel therapeutic targets.

Disclosure:

N (SNP, SS, AZ, AVJ, ZA) S (AK/VA, NIH 1R01EY032149-01)