Ocular Microbiology and Immunology Group
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2024 OMIG Abstract

Harnessing the Power of Macrophage Secretome to Combat Corneal Scarring Following Microbial Keratitis

Gink Yang^1,2, Andrew Wang^1,2, Manisha Shah^1,2, and Mark Daniell<sup>1,2

1</sup>Centre for Eye Research Australia (CERA), East Melbourne, Victoria, Australia;
²Department of Surgery (Ophthalmology), Medicine Dentistry and Health Science,
University of Melbourne, Melbourne, Victoria, Australia

Purpose: Microbial keratitis is a leading cause of blindness worldwide, characterized by painful ulceration and scarring of the cornea. Delays in diagnosis and rise in antibiotic resistance have reduced the effectiveness of antibiotics, leaving the cornea at risk of prolonged tissue damage. Given that the fibrotic process is mediated by multiple factors, previous studies targeting a single pro-fibrotic mediator such as using TGF-β1 blocker failed to reduce scarring. Resident corneal macrophages (Mφ) are known to secrete factors that regulate inflammation and maintain transparency of the cornea, thereby regulating tissue repair and fibrosis. Collectively named as the macrophage secretome (MφS), we aim to investigate whether treatment using MφS could reduce fibrosis during corneal scarring.

Methods: In our in vitro study, MφS collected from THP1-derived macrophages was used to treat fibrotic primary keratocytes in culture. The expression of fibrosis and corneal clarity related genes in the keratocytes were analyzed using RT-qPCR. Conversely, secretome collected from keratocytes-derived myofibroblasts was used to treat THP1 monocytes. The level of key immune regulators in the monocytes was analyzed using ELISA.

Results: MφS released by monocyte-derived macrophages activated at various levels had differential effect on fibrosis suppression, while maintaining stromal integrity necessary for corneal clarity.

Conclusions: Targeting fibrosis using MφS at different stages has the potential to suppress scarring in the cornea.


Disclosure:

S