Microscopic mammalian retinal pigment epithelium lesions induce widespread proliferation with differences in magnitude between center and periphery

[摘要] Purpose: The vertebrate retina developsfrom the center to the periphery. In amphibians and fish the retinalmargin continues to proliferate throughout life, resulting in retinalexpansion. This does not happen in mammals. However, some mammalianperipheral retinal pigment epithelial (RPE) cells continue to divide,perhaps as a vestige of this mechanism. The RPE cells are adjacent tothe ciliary margin, a known stem cell source. Here we test thehypothesis that peripheral RPE is fundamentally different from centralRPE by challenging different regions with microscopic laser burns andcharting differential responses in terms of levels of proliferation andthe regions over which this proliferation occurs. Methods: Microscopic RPE lesions wereundertaken in rats at different eccentricities and the tissue stainedfor proliferative markers Ki67 and bromodeoxyuridine (BrdU) and theremodeling metalloproteinase marker 2 (MMP2). Results: All lesions produced local RPEproliferation and tissue remodeling. Significantly more mitosisresulted from peripheral than central lesions. Unexpectedly, singlelesions also resulted in RPE cells proliferating across the entireretina. Their number did not increase linearly with lesion number,indicating that they may be a specific population. All lesions repairedand formed apparently normal relations with the neural retina. RepairedRPE was albino. Conclusions: These results highlightregional RPE differences, revealing an enhanced peripheral repaircapacity. Further, all lesions have a marked impact on both local anddistant RPE cells, demonstrating a pan retinal signaling mechanismtriggering proliferation across the tissue plane. The RPE cells mayrepresent a distinct population as their number did not increase withmultiple lesions. The fact that repairing cells were hypopigmented isof interest because reduced pigment is associated with enhancedproliferative capacities in the developing neural retina.

[学科分类] 生物化学/生物物理