Intraretinal pigmented cells in retinal degenerative disease

Purpose Invasion of pigmented cells into the retina occurs in retinal degenerative diseases, such as macular telangiectasia type 2 (MacTel) and retinitis pigmentosa (RP). These intraretinal pigmented cells may be derived from the retinal pigment epithelium (RPE), but differences and similarities between intraretinal pigmented cells and RPE have so far not been well characterised. Clinicopathologic case report. Method Here, we compared intraretinal pigment cells with RPE cells by immunohistochemistry. Immunohistological stains for classic RPE markers (RPE65, CRALBP and KRT18) and blood vessel markers (lectin and collagen 4) were done on sections from postmortem eye tissue from two MacTel donors, an RP donor and a control donor. Main outcome measures Presence of specific immunohistochemistry markers on intraretinal pigmented and RPE cells. Results We found that intraretinal pigmented cells did not express RPE65 and CRALBP, with a small subset expressing them weakly. However, they all expressed KRT18, which was also present in normal RPE cells. Interestingly, we also found clusters of KRT18-positive cells in the retina that were not pigmented. Conclusions Our findings suggest that RPE cells invading the retina dedifferentiate (losing classic RPE markers) and can be pigmented or unpigmented. Therefore, the number of RPE cells invading the retina in retinal degenerative disease may be underappreciated by funduscopy.