Abstract
Purpose::
Sialoadhesin, a member of the sialic acid binding Ig-like lectin (Siglec) family, is a macrophage-restricted cellular interaction molecule that binds sialylated ligands. It is strongly expressed on macrophages in lymph nodes, bone marrow, and spleen and moderately expressed on resident macrophages in the liver, gut, and lung, but it is supposedly not expressed on quiescent microglial cells in the CNS. The purpose of the present study was to examine whether and when sialoadhesin is expressed in mouse models of Retinitis Pigmentosa.
Methods::
Distribution of sialoadhesin was analyzed by immunohistochemistry in retinas obtained from rd1 mice, postnatal days 7 to 21 (P7-P21) and rds mice (P8-P30). Specific markers of retinal cell types and structures (cellular retinal-binding protein, CRALBP; CD11b; and CD45) were used to identify cells expressing sialoadhesin.
Results::
In normal mouse retinas, no sialoadhesin-expressing cells were observed in the outer nuclear layer (ONL) at any time point. In rd1 mice, weakly labeled cells were observed in the central retina at P11 in the outer plexiform layer sending out short processes into the ONL. From P12 and onwards, increasing numbers of labeled cells were seen over the ONL, initially in the central retina, but with time throughout the retina. A few cells were seen occasionally also in the subretinal space. In rds mouse retinas, only a few sialoadhesin-positive cells were observed mainly in the subretinal space from P10.
Conclusions::
Sialoadhesin-expressing cells are observed in association with photoreceptor cell loss, in both, rd1 and rds mice. The morphology of the labeled cells and their distribution suggest that they correspond to activated resident microglial cells and/or hematogenous microglial precursors recruited to the sites of photoreceptor degeneration. Nearly complete loss of rod cells occurs within the first postnatal weeks in rd1 mice, whereas in rds mice, it occurs over the course of several months. Although microgliosis is not the initiator of cell death, the fact that activated microglial cells express sialoadhesin during the early stages of the degenerative process in rd1 mice, suggests that they are likely to mediate pro-inflammatory signals. Such signals could accelerate the loss of rod cells and/or contribute to the secondary loss of cones observed in this model.
Keywords: microglia • retinal degenerations: cell biology • inflammation