Abstract
Abstract: :
Purpose: Microarray analysis of an αA–crystallin gene knock–out mouse indicated that preproglucagon transcripts are present in the mouse lens. The preproglucagon transcript encodes a propeptide that gives rise to the peptides glucagon, glucagon–like peptide 1 (GLP–1), and glucagon–like peptide 2 (GLP–2). This study was conducted to determine which of the encoded glucagon family peptide receptors are present in various ocular tissues and to elucidate the ocular roles for peptides whose traditionally recognized targets are the liver and digestive tract. Methods: Total RNA was isolated from mouse lens, mouse retina, and cultured human RPE cells (ARPE–19). RT–PCR was carried out using total RNA samples with primers specific for glucagon, GLP–1, and GLP–2 receptors based upon human and mouse GenBank sequences. Immunohistochemistry (IHC) was performed on whole eye cryosections. Cell proliferation assays were conducted by colorimetric measurements of the reduction of WST–8. Results: RT–PCR of total RNA from mouse lens, mouse retina, and human ARPE–19 cells showed the presence of transcripts for the glucagon receptor and GLP–2 receptor, but not the GLP–1 receptor. The receptors for glucagon and GLP–2 were detected by IHC in the corneal epithelium and endothelium, the lens epithelial layer, and throughout various layers of the retina. GLP–1 receptors were not detectable in these tissues. The proliferation of ARPE–19 cells in culture was unaffected by the administration of GLP–2. Conclusions: Receptors for glucagon and GLP–2 are present in lens, cornea, and throughout the retina. GLP–2 receptors have a very limited anatomical distribution; their presence in the eye is therefore noteworthy. The actions of GLP–2 in ocular tissues may be novel, since the cell proliferation induced by GLP–2 in other tissues is absent.
Keywords: retinal pigment epithelium • cornea: basic science