Researchers have come a bit closer to figuring out the primary cause of fibrotic posterior capsular opacification (PCO), an undesirable outcome of cataract surgery. They report a cascade of events triggered by surgical trauma, starting with the transformation of remnant lens epithelial cells (LECs) into signaling centers that promote inflammation.1
And while the researchers haven’t connected all the dots, they speculate that postsurgical inflammation may play a key role in the onset of PCO, which affects a wide range of adults (25%-70% of patients) and nearly 100% of children 10 years after surgery.
Starting with mice. To understand the mechanisms by which ocular trauma results in fibrotic PCO, the researchers surgically removed the lens fiber cells in mice, leaving behind the lens capsule and attached LECs. They then compared the levels of all mRNAs expressed by LECs immediately following surgery and 24 hours later.
While, as expected, many genes associated with fibrosis are upregulated, the researchers’ comparison revealed that LECs robustly activate the innate immune response within hours of cataract surgery.
An unexpected finding. “That lens cells have the capability of becoming signaling centers for ocular inflammation was surprising, because the lens is classically thought of as an immune-privileged site,” said Melinda K. Duncan, PhD, at the University of Delaware in Newark. “But here, lens cells are making huge amounts of cytokines associated with the innate immune system.”
Two implications to consider. First, if the remnant LECs prove to be primary drivers of postsurgical inflammation, they could be targeted to directly reduce this side effect of surgery, Dr. Duncan said. “Second, if we can shut down the inflammatory response by lens epithelial cells, we can test the idea that inflammation is a trigger for fibrotic PCO. If that is the case, inhibiting that inflammation could be an approach to reducing fibrotic PCO.”
Up next. The researchers hope to identify the precise mechanism by which surgery induces this process. Their most recent results have shown the likely upstream trigger is a signaling cascade initiated immediately after surgery, leading to the activation of “immediate early response” transcription factors.
“We anticipate that this trigger will involve a receptor that we could anticipate blocking clinically,” Dr. Duncan said. However, she said, researchers are “likely two to five years away” from identifying the relevant pathways. “Our goal is to identify a therapy that could be instilled into the eye during surgery to block this cascade.”
1 Jiang J et al. Invest Ophthalmol Vis Sci. 2018;59(12):4986-4997.
Relevant financial disclosures—Dr. Duncan: None.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Chen Singapore A*STAR Biomedical Research Council: S; Singapore National Research Foundation: S; Singapore Ministry of Education: S; Singapore Ministry of Health: S.
Dr. Duncan NEI: S.
Dr. Eslani None.
Dr. Tam None.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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