Carcinoembryonic antigen-related cell adhesion molecule 1 regulates laser-induced choroidal neovascularization

Abstract

Purpose : The molecular pathogenesis of choroidal neovascularization (CNV), an angiogenic process that contributes critically to vision loss in age-related macular degeneration (AMD), is unclear. Here, we investigated whether carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) contributes to CNV formation. Thus, we characterized the expression of CEACAM1 in the eye and studied the effects Ceacam1 deletion in mice under physiologic and pathologic (laser-induced CNV) conditions.

Methods : Ocular CEACAM1 expression was analyzed by immunohistochemistry, flow cytometry (FACS) and quantitative (q)PCR. Ocular morphology in Ceacam knockout (Ceacam^-/-) and C57BL/6J wild type (WT) littermates was studied by light microscopy, immunohistochemistry, FITC-dextran perfusions and in vivo imaging. Inner and outer nuclear layer (INL/ONL) thickness and the number of ionized calcium-binding adaptor molecule 1 (IBA1)-positive myeloid cells in the retina were determined. CNVs were induced with a frequency-doubled Nd:YAG laser. Then the CNVs were visualized by in vivo angiography and CNV area was determined by collagen IV staining of choroidal flatmounts. CNV-associated myeloid cells were counted on IBA1-stained choroidal flatmounts.

Results : Immunohistochemical and FACS analyses showed strong CEACAM1 expression in retinal and choroidal endothelial cells. FACS analyses furthermore revealed expression in a subset of CD11b-positive myeloid cells. Semithin sections from adult Ceacam^-/- vs. WT eyes showed no obvious alterations of the retinal morphology and in INL/ONL thickness. Retinal and choroidal vessels appeared normal. IBA1-positive myeloid cells in adult retinae revealed no significant differences between Ceacam^-/- and WT littermates. However, Ceacam^-/- mice displayed significantly smaller laser-induced CNV areas (p < 0.001) and significantly less CNV-associated IBA1-positive cells (p < 0.05) compared to WT littermates.

Conclusions : CEACAM1 is expressed in retinal and choroidal endothelial and a subset of CD11b-positive myeloid cells. Ceacam1 deletion does not alter ocular morphology. However, it does result in reduced angiogenesis/accumulation of IBA1-positive cells following laser-induced CNV. Thus, CEACAM1 may be a promising target to inhibit angiogenesis in neovascular eye diseases.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.