Apoptosis inhibitor of macrophages/CD5L enhances phagocytosis in the trabecular meshwork cells and regulates ocular hypertension
Journal of cellular physiology(2023)
摘要
The trabecular meshwork (TM) cells of the eye are important for controlling intraocular pressure (IOP) and regulating outflow resistance in the aqueous humor. TM cells can remove particles and cellular debris by phagocytosis, decreasing both outflow resistance and IOP. However, the underlying mechanisms remain unclear. Here, we investigate whether apoptosis inhibitor of macrophages (AIM), which mediates the removal of dead cells and debris in renal tubular epithelial cells, regulates the phagocytic capacity of TM cells. In vitro experiments revealed that CD36, the main receptor for AIM, colocalized with AIM in human TM cells; additionally, phagocytosis was stimulated when AIM was provided. Furthermore, in a mouse model with transient IOP elevation induced by laser iridotomy (LI), removal of accumulated iris pigment epithelial cells or debris in the TM and recovery of IOP to baseline levels were delayed in AIM(-/-) mice, compared with control mice. However, treatment with AIM eyedrops rescued AIM(-/-) mice from the elevated IOP after LI. Since AIM is a protein known to inhibit macrophage apoptosis, we additionally verified its involvement in macrophage removal of cellular debris and IOP. There were no statistically significant differences in the number of macrophages between control mice and AIM(-/-) mice in the TM. Additionally, we confirmed the rescue effect of the rAIM eyedrops after macrophages had been removed by clodronate liposomes. Therefore, AIM plays an important role in regulating the phagocytic capacity of TM cells, thereby affecting outflow resistance. Our results suggest that drugs targeting the phagocytic capacity of TM cells via the AIM-CD36 pathway may be used to treat glaucoma.
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关键词
apoptosis inhibitor of macrophage,glaucoma,intraocular pressure,phagocytosis,trabecular meshwork cells
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