Search Results

Abstract

PURPOSE: To characterize the extracellular vesicle protein cargo in the aqueous humor and plasma of patients with ocular toxoplasmosis.
METHODS: Aqueous humor and plasma were collected from six patients with active ocular toxoplasmosis and six patients with cataract. Extracellular vesicles were isolated, and western blotting and mass spectrometry were performed for protein analysis.
RESULTS: All plasma samples from patients with ocular toxoplasmosis and cataract were positive for the tetraspanins CD63 and TSG101. However, the aqueous humor from patients with ocular toxoplasmosis was positive only for CD63. Sixty-seven new unreported proteins were identified in the aqueous humor and plasma of patients with the ocular toxoplasmosis and cataract. Of the 67 proteins, 10 and 7 were found only in the cataract and ocular toxoplasmosis groups, respectively. In general, these proteins were involved in immune system activation and retina homeostasis and were related to infections and retina-associated diseases. Conclusion: The distinct protein signatures between ocular toxoplasmosis and cataract may be helpful in the differential diagnosis of ocular toxoplasmosis. However, more studies are needed to better understand the role of these proteins in the pathogenesis of ocular toxoplasmosis.

Keywords: Extracellular vesicles; Proteomics; Toxoplasma gondii; Ocular toxoplasmosis, Aqueous humor; Plasma; Liquid biopsy

Abstract

Corneal blindness affects more than 12 million individuals worldwide; however, the availability of human donor corneas meets only a small fraction of the demand. Porcine corneal xenotransplantation represents a promising alternative because of the cornea's immune privilege and the anatomical similarities between human and porcine corneas. However, the galactose-α1,3-galactose antigen expressed on porcine cells induces hyperacute rejection through the activation of human anti-Gal antibodies, complement pathways, and innate immune cell infiltration. This review summarizes the mechanisms underlying corneal immune privilege and contrasts them with galactose-α1,3-galactose-mediated rejection pathways. In addition, it evaluates five major mitigation strategies: GGTA1-knockout pigs, enzymatic α-galactosidase treatment, RNA interference, decellularization, and immunosuppressive approaches, including CD40-CD154 blockade and topical tacrolimus. Preclinical studies have demonstrated that GTKO corneas can maintain transparency for longer than 1 year, whereas decellularized matrices preserve corneal architecture while exhibiting low antigenicity. These findings support the future clinical translation of porcine corneal xenotransplantation.

Keywords: Corneal transplantation; Xenotransplantation; Graft rejection; Galactose; Immunosuppressive agents.