Abstract
Purpose :
Human corneal endothelial cells (hCECs) have limited regenerative capacity under normal conditions, leading to corneal decompensation after significant loss of these cells. Mesenchymal stem/stromal cells (MSCs) are promising for stem cell therapy due to their self-renewal capability, potential to differentiate into various cell types, and their immunomodulatory and anti-inflammatory effects. We propose that intracameral delivery of human bone marrow-derived MSCs (hBM-MSCs) could protect and regenerate CECs in a mouse model of endothelial damage induced by Benzalkonium chloride (BAK) injection.
Methods :
The study was conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and approved by the ACUC and the IBC Committee. We used 24 six-to-eight-week-old C57BL/6J mice, divided into three groups. All were administered 5 μL intracameral benzalkonium chloride (BAK). On the second day post-exposure, group 3 received 100,000 hBM-MSCs in 5 μL intracamerally, while groups 1 and 2 were given intracameral injections of phosphate-buffered saline (PBS) and culture medium (CM), respectively, as controls. All injections were performed with a 32-gauge needle. We evaluated corneal opacities and central thickness using slit lamp imaging and anterior segment optical coherence tomography (AS-OCT), followed by immunohistochemical studies after one month (Figures 1 and 2). We also included a separate group of 10 mice to monitor the presence of MSCs after the injection.
Results :
In the MSC-treated group, there was a significant reduction in corneal opacity levels compared to controls (p = 0.005). The MSC group also had a significantly thinner central corneal thickness (CCT) averaging 77.3±3.70 µm (p < 0.001), and less fibrosis (p=0.03). No significant differences were found between the control groups (p > 0.05). Furthermore, MSC presence was confirmed on the endothelial cells up to one week post-injection by CD73 staining.
Conclusions :
MSCs have been shown to promote healing and potentially regenerate damaged endothelial cells. Looking forward, enhanced MSC therapy might obviate the need for endothelial keratoplasty, opening new avenues for research in human studies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.