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F. Lebrun–Julien, Y. Zhou, S. Chemtob, A. Di Polo; Lysophosphatidic Acid Receptor Type–1 (LPA1) Expression in Normal and Glaucomatous Adult Rat Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1319.
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Purpose: Lysophosphatidic acid (LPA) is a bioactive phospholipid that regulates a plethora of cellular processes, including gene expression, cell survival and neurite retraction. The biological role of LPA signaling in the intact and injured central nervous system remains undefined. To identify the retinal neurons responsive to LPA, we investigated the endogenous expression of the LPA receptor type–1 (LPA1) in young and aging normal rat retinas, as well as in retinas from glaucomatous eyes. Methods: Unilateral, chronic elevation of intraocular pressure (IOP) was induced by injection of hypertonic saline solution into an episcleral vein. The expression of LPA1 was examined by immunocytochemistry using a LPA1 antibody on retinal cross sections. Double labeling with anti–LPA1 and cell–specific markers was performed to identify LPA1–positive cells. Results: Robust LPA1 immunostaining was observed in the vast majority (>95%) of cells in the ganglion cell layer in normal retinas from young adult (∼ 1 mo) and aging (>10 mo) rats. Co–labeling experiments with anti–LPA1 and retrograde tracers, such as Fluorogold or DiI, confirmed LPA1 localization in retinal ganglion cells (RGCs). Displaced amacrine cells present in the ganglion cell layer, identified with a calretinin antibody, also expressed the receptor LPA1. Furthermore, staining with anti–LPA1 and a nuclear marker (DAPI) demonstrated LPA1 receptor localization in neuronal nuclei in both young and aging retinas. Strong LPA1 staining in the nucleus persisted in RGCs and amacrine cells at 5 weeks after ocular hypertension surgery. Conclusions: The abundant expression of LPA1 in adult retinal neurons suggests that LPA plays a role in their normal function and maintenance. The nuclear localization of the LPA1 receptor is consistent with an LPA intracrine mode of action. Importantly, the translocation of LPA1 to other cellular compartments in glaucoma may be linked to the neuronal response to hypertension damage.
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