THE HUMAN TISSUE PROTEOMES

Eye



The Tissue atlas is based on immunohistochemical staining of tissue microarrays from 44 different normal tissue types. In addition to the standard setup, extended tissue profiling is performed for selected proteins, to give a more complete overview on where the protein is expressed. Extended tissue samples include mouse brain, human lactating breast, eye, and additional samples of adrenal gland, skin and brain. For eye, full section of eye and 1 mm diameter cores of retina were used.

The full list of proteins analyzed in eye and retina is found in Table 1.


Eye


The eye globe is covered by a fibrous coat which includes an anterior translucent surface called cornea. Light enters the eye through the pupil, behind the cornea, and is refracted by the lens, a transparent disc suspended by muscular fibers behind the pupil. The refracted light is focused on the retina, the innermost layer of the eye which transforms light into nerve signals that are then transmitted by the optical nerve to the brain. A vascular layer, called choroid, provides nutrients to the cells of the eye. An example of a protein essential for the structure and function of lens is crystallin B2 (CRYBB2) (Figure 1). It is a major component of lens fiber and maintains transparency and refractive index of the lens.

Figure 1. Immunohistochemical staining of human eye using an antibody toward CRYBB2 shows strong positivity in lens.


Retina


The layer of neural retina nearest the choroid contains photoreceptor cells: rods and cones. Rods register presence of light and allow night vision while cones register red, green and blue colors and allow color vision. Between the photoreceptors and choroid is a layer of pigment epithelium which provides nutrients and protection against oxidative stress to the photoreceptor cells. Nerve signals are transmitted from the photoreceptors to cells in the inner nuclear and ganglion cell layers through nerve fibers in the inner and outer plexiform layers, and are finally collected in the optical nerve. The protein cGMP phosphodiesterase (PDE6B) is expressed in the outer segments of photoreceptor cells and is involved in transmission and amplification of visual signals (Figure 2).

Figure 2. Immunohistochemical staining of human retina using an antibody toward PDE6B shows strong positivity in outer segments of photoreceptor cells.


Table 1. The following 53 genes have been analyzed using extended eye (10 genes) and retina (43 genes) tissue samples.

Gene

Gene description

Tissue

Staining pattern

BFSP1 Beaded filament structural protein 1, filensin Eye Moderate cytoplasmic positivity was observed in lens.
BFSP2 Beaded filament structural protein 2, phakinin Eye Strong positivity was observed in lens.
BTBD6 BTB (POZ) domain containing 6 Eye Strong positivity was observed in lens.
CRYBA4 Crystallin, beta A4 Eye Strong positivity was observed in lens in eye.
CRYBB2 Crystallin, beta B2 Eye Strong staining was observed in the lens.
GJA3 Gap junction protein, alpha 3, 46kDa Eye Strong positivity was observed in lens.
KRT12 Keratin 12, type I Eye Strong cytoplasmic positivity was observed in the cornea.
LGSN Lengsin, lens protein with glutamine synthetase domain Eye Strong positivity was observed in lens. Remaining parts of the eye were negative.
MIP Major intrinsic protein of lens fiber Eye Strong positivity was observed in the lens.
OPTC Opticin Eye Strong staining was observed in vitreous of the eye.
AIPL1 Aryl hydrocarbon receptor interacting protein-like 1 Retina Strong cytoplasmic and nuclear positivity was observed in photoreceptor cells.
ARMS2 Age-related maculopathy susceptibility 2 Retina Moderate cytoplasmic positivity was observed in outer and inner plexiform layers.
BEST1 Bestrophin 1 Retina Strong staining was observed in basal membrane of retinal pigment epithelium.
CDHR1 Cadherin-related family member 1 Retina Strong cytoplasmic and membranous positivity was observed in photoreceptor outer segments.
CNGB3 Cyclic nucleotide gated channel beta 3 Retina Strong staining of basal membrane in photoreceptor layer. Weak cytoplasmic staining in a few cells in several other layers of retina.
CRB1 Crumbs family member 1, photoreceptor morphogenesis associated Retina Moderate cytoplasmic positivity was observed in photoreceptor cells and in outer plexiform layer.
CRX Cone-rod homeobox Retina Strong nuclear positivity was observed in photoreceptor cells.
EFEMP1 EGF containing fibulin-like extracellular matrix protein 1 Retina Strong cytoplasmic staining in rods, outer and inner plexiforms layers and nerve fiber layer.
GNAT1 Guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 1 Retina Strong cytoplasmic positivity was observed in rod segments.
GNGT1 Guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 Retina Strong cytoplasmic positivity was observed in rods.
GNGT2 Guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 2 Retina Strong cytoplasmic positivity was observed in cones.
GRK1 G protein-coupled receptor kinase 1 Retina Strong cytoplasmic positivity was observed in photoreceptor cells.
GRM6 Glutamate receptor, metabotropic 6 Retina Strong cytoplasmic positivity was observed in nerve fibers.
GUCA1A Guanylate cyclase activator 1A (retina) Retina Strong cytoplasmic positivity was observed in photoreceptor layer and outer plexiform layer. Nerve fiber layer showed moderate staining.
IMPG1 Interphotoreceptor matrix proteoglycan 1 Retina Strong cytoplasmic positivity was observed in photoreceptor cells.
IMPG2 Interphotoreceptor matrix proteoglycan 2 Retina Strong cytoplasmic positivity was observed in segments of photoreceptor cells.
MYO3A Myosin IIIA Retina Moderate cytoplasmic positivity was observed in photoreceptor cells and rare ganglion cells. Remaining layers in retina were weakly stained or negative.
NPVF Neuropeptide VF precursor Retina Strong cytoplasmic positivity was observed in nerve fibers.
NRL Neural retina leucine zipper Retina Strong nuclear positivity was observed in rods.
OPN1SW Opsin 1 (cone pigments), short-wave-sensitive Retina Strong cytoplasmic positivity was observed in outer segments of rods.
OPN4 Opsin 4 Retina Strong cytoplasmic positivity was observed in nerve fibers in outer and inner plexiform layers and nerve fiber layer.
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Relevant links and publications


Uhlén M et al, 2015. Tissue-based map of the human proteome. Science
PubMed: 25613900 DOI: 10.1126/science.1260419

Yu NY et al, 2015. Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium. Nucleic Acids Res.
PubMed: 26117540 DOI: 10.1093/nar/gkv608

Fagerberg L et al, 2014. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics.
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600