Expression of Olfactory Signaling Genes in the Eye

Abstract

PurposeTo advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors.MethodsTotal RNA from the mouse cornea was subjected to next-generation sequencing using the Illumina platform. The data was analyzed with TopHat and CuffLinks software packages. Expression of a representative group of genes detected by RNA-seq was further analyzed by RT-PCR and in situ hybridization using RNAscope technology and fluorescent microscopy.ResultsWe generated more than 46 million pair-end reads from mouse corneal RNA. Bioinformatics analysis revealed that the mouse corneal transcriptome reconstructed from these reads represents over 10,000 gene transcripts. We identified 194 GPCR transcripts, of which 96 were putative olfactory receptors. RT-PCR analysis confirmed the presence of several olfactory receptors and related genes, including olfactory marker protein and the G protein associated with olfaction, Gαolf. In situ hybridization showed that mRNA for olfactory marker protein, Gαolf and possibly some olfactory receptors were found in the corneal epithelial cells. In addition to the corneal epithelium, Gαolf was present in the ganglionic and inner nuclear layers of the retina. One of the olfactory receptors, Olfr558, was present primarily in vessels of the eye co-stained with antibodies against alpha-smooth muscle actin, indicating expression in arterioles.ConclusionsSeveral species of mRNA encoding putative olfactory receptors and related genes are expressed in the mouse cornea and other parts of the eye indicating they may play a role in sensing chemicals in the ocular environment.

GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration

“…Expression of the OR52B4 gene was present in the retina, optic nerve and choroid (Supplementary Table S4). The identification of olfactory gene expression in the eye is relatively new, but not surprising, as21 recently published expression profiling of a number of olfactory receptors (olfr) in mouse cornea, retina and choroid. Their analysis of eye tissue expression confirmed the presence of many olfr, with one of them, olfr547 representing a homolog of the human OR52B4 gene (85% identity).…”

‘Smelling’ the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus

“…*P < 0.05, **P < 0.01, ***P < 0.001. [19,20,[32][33][34]. Accumulating molecular evidence indicates that these receptors are widely expressed outside the olfactory system, with some known roles including muscle regeneration, regulation of gut motility, sperm chemotaxis, renal function and embryogenesis [35].…”

“…For example Gaolf, which transmits signals from ORs to downstream effectors, was shown to be expressed in the brain, placenta, kidney and eye [20,33,40,41]. AC3 has been described in kidney and in spermatozoa [42], and CNG2 in the cochlea [38], in vascular tissue [39] and in the brain [43,44].…”

G Protein–Coupled Receptor (GPCR) Expression in Native Cells: “Novel” endoGPCRs as Physiologic Regulators and Therapeutic Targets

“…As shown by the studies in Tables 2 and 3, most efforts have focused on the use of array-or PCR-based methods and have emphasized the expression of nonchemosensory GPCRs. Recent studies, however, have identified chemosensory receptor expression in tissues not typically thought to be in involved in sensation (Reimann et al, 2012;Foster et al, 2014a,b;Pronin et al, 2014;Rajkumar et al, 2014;Malki et al, 2015). With the discovery of smallmolecule metabolites [in some cases, products of microbiota (e.g., Natarajan and Pluznick, 2014)] that interact with GPCRs and that may have been considered odorants or tastants, the distinction between chemosensory and nonchemosensory GPCRs is blurring.…”