This technology provides pharmaceutical and health food compositions for preventing and treating keratitis, using exosomes secreted by EGF-treated M1 or M2a macrophages as the active ingredient. It also includes a method for inhibiting angiogenesis by applying these exosomes to corneal endothelial cells. Exosomes released by macrophages, whose inflammation has been mitigated by EGF, suppress both inflammation and neovascularization in surrounding corneal endothelial cells.
The cornea is a transparent, avascular tissue exposed to the environment, making it vulnerable to trauma and scratches. Severe damage can lead to keratitis and corneal neovascularization, threatening vision. While EGF has been used in ophthalmology for corneal epithelial regeneration and sensory nerve recovery, its role in mediating anti-inflammatory and anti-angiogenic effects between deep-seated macrophages and corneal endothelial cells had not been previously established.
This technology is based on the finding that EGF reduces IL-1β and IL-6 expression in M1 macrophages, and that their exosomes lower the expression of VCAM-1, ICAM-1, VEGF, MMP-2, MMP-9, and PDGF in corneal endothelial cells. Furthermore, exosomes from EGF-treated M2a macrophages promote both anti-inflammatory effects and cell proliferation in damaged corneal endothelial cells. The formulation can be developed as eye drops, ophthalmic ointments, ocular inserts, or injections. Applicable to treatments for infectious and non-infectious keratitis, as an adjunct for inhibiting neovascularization after corneal transplantation, and for managing corneal damage in long-term contact lens wearers, this approach delivers exosomes rather than cells to simultaneously manage corneal inflammation and vascular infiltration while aiding the recovery of damaged endothelial cells.
This invention was developed with support from the Ministry of Science and ICT for strategies to treat ocular surface immune inflammation using AITR stimulation technology in immune cells.
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