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, thymus 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 enveloped in a fibrous corneoscleral layer. The anterior portion includes a translucent surface called the cornea, while the rest is made up by sclera, a white-coloured fibrous layer to which the outer eye muscles are attached. The front of the cornea is covered with a non-keratinized stratified corneal epithelium. Keratin 12 (KRT12) is a protein expressed in the corneal epithelium and may be involved in the maintenance of its normal function and structural integrity (Figure. 1).


Figure 1. Immunohistochemical staining of human eye using an antibody toward KRT12 shows strong positivity in corneal epithelium.

Underneath the corneoscleral coat lies a vascular coat, which consists of choroid, ciliary body and iris. The choroid contains blood vessels and melanin pigment and its main function is to provide nutrients to the cells of the eye. The pupil is a round gap in the middle of the iris and the size of the pupil affects the amount of light that enters the eye.

Light is refracted by the lens, a transparent disc suspended by ciliary muscle fibers. Elongated fiber cells are the predominant component of the lens while the anterior side is lined with epithelial cells. An example of a protein essential for the structure and function of the lens is crystallin B2 (CRYBB2) (Figure 2). It is a major component of lens fiber and maintains transparency and refractive index of the lens. 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.


Figure 2. Immunohistochemical staining of human eye using an antibody toward CRYBB2 shows strong positivity in lens.

The space between retina and lens is filled up by a transparent gelatinous mass called the vitreous humour. Opticin (OPTC) is a protein expressed in the vitreous humour (Figure 3). It may bind collagen fibrils and play an important role in their structural organisation.


Figure 3. Immunohistochemical staining of human eye using an antibody toward OPTC shows strong positivity in vitreous of the eye.


Retina


The layer of neural retina nearest the choroid contains photoreceptor cells: rods and cones. Photoreceptor cells have an elongated shape and the largest proportion of the cytoplasm form segments, divided into inner and outer segments, that point in the direction of the choroid. The inner segment contains organelles that are essential for cell metabolism. The transformation of light into intracellular molecular signals takes place in the outer segments. Rods register presence of light and allow night vision while cones register red, green and blue colors and allow color vision. Rhodopsin (RHO) is the transmembrane protein that initiates the visual transduction cascade in rods and is expressed specifically in rods (Figure 4). G protein subunit gamma transducin 2 (GNGT2) is one of the signal proteins that regulate phototransduction and, unlike the closely related GNGT1 that is rod specific, it is expressed only in cones (Figure 5).


Figure 4. Immunohistochemical staining of human retina using an antibody toward RHO shows strong positivity in outer segments of rods.


Figure 5. Immunohistochemical staining of human retina using an antibody toward GNGT2 shows strong cytoplasmic positivity in cones.


Between the photoreceptors and choroid is a layer of pigment epithelium which provides nutrients and protection against oxidative stress to the photoreceptor cells. Photoreceptor cells are associated with the pigment epithelium via the outer segments. The nuclei of photoreceptors comprise the outer nuclear layer. 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.

Müeller’s glia maintain the structural integrity of the retina by stretching across all layers, from the nerve fibers nearest the inside of eye to the outer limiting membrane. The outer limiting membrane is a row of cell-junctions located where the inner and outer segments of photoreceptors connect. Here, Müeller glia connect to each other and to the photoreceptor cells. Crumbs 2 (CRB2) is one of the proteins that comprise the Crumbs cell polarity complex, which is essential for the establishment of cell-cell junctions of epithelial cells. In retina, CRB2 is expressed in the outer limiting membrane (Figure 6).


Figure 6. Immunohistochemical staining of human retina using an antibody toward CRB2 shows strong positivity in the outer limiting membrane.

Table 1. The following 94 genes have been analyzed using extended eye (20 genes) and retina (74 genes) tissue samples.

Gene Gene description Tissue Staining pattern
BFSP1 Beaded filament structural protein 1 Eye Moderate cytoplasmic positivity was observed in lens.
BFSP2 Beaded filament structural protein 2 Eye Strong positivity was observed in lens.
BTBD6 BTB domain containing 6 Eye Strong positivity was observed in lens.
CH507-152C13.3 Eye Staining in lens.
COL9A2 Collagen type IX alpha 2 chain Eye Staining in vitreous humor.
COL9A3 Collagen type IX alpha 3 chain Eye Staining in vitreous humor of the eye.
CRYAA Crystallin alpha A Eye Staining in lens.
CRYBA1 Crystallin beta A1 Eye Staining in lens.
CRYBA2 Crystallin beta A2 Eye Strong staining in lens.
CRYBA4 Crystallin beta A4 Eye Strong positivity was observed in lens in eye.
CRYBB1 Crystallin beta B1 Eye Staining in lens.
CRYBB2 Crystallin beta B2 Eye Strong staining was observed in the lens.
CRYBB3 Crystallin beta B3 Eye Staining in lens.
GJA3 Gap junction protein alpha 3 Eye Strong positivity was observed in lens.
GJA8 Gap junction protein alpha 8 Eye Staining of lens.
KRT12 Keratin 12 Eye Strong cytoplasmic positivity was observed in the corneal epithelial cells.
LGSN Lengsin, lens protein with glutamine synthetase domain Eye Strong positivity was observed in lens. Remaining parts of the eye were negative.
LUM Lumican Eye Staining in cornea.
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 Positivity in photoreceptor cells.
ANO2 Anoctamin 2 Retina Positivity in outer plexiform layer.
ARMS2 Age-related maculopathy susceptibility 2 Retina Positivity in outer and inner plexiform layers.
ARR3 Arrestin 3 Retina Staining in cones.
BEST1 Bestrophin 1 Retina Positivity in basal membrane of retinal pigment epithelium.
CABP5 Calcium binding protein 5 Retina Positivity in ganglion cells and cells in inner nuclear layer.
CACNA1F Calcium voltage-gated channel subunit alpha1 F Retina Positivity in photoreceptor cells segments.
CDHR1 Cadherin related family member 1 Retina Positivity in photoreceptor cell outer segments.
CLUL1 Clusterin like 1 Retina Positivity in rods.
CNGB3 Cyclic nucleotide gated channel beta 3 Retina Positivity in outer liming membrane.
COL9A1 Collagen type IX alpha 1 chain Retina Positivity in cones.
CPLX4 Complexin 4 Retina Positivity in inner plexiform layer.
CRABP1 Cellular retinoic acid binding protein 1 Retina Positivity in inner nuclear layer and nerve fibers.
CRB1 Crumbs 1, cell polarity complex component Retina Positivity in photoreceptor cells and in outer plexiform layer.
CRB2 Crumbs 2, cell polarity complex component Retina Positivity in outer limiting membrane.
CRX Cone-rod homeobox Retina Positivity in photoreceptor cells.
EFEMP1 EGF containing fibulin like extracellular matrix protein 1 Retina Positivity in rods, outer and inner plexiform layers and nerve fiber layer.
GNAT1 G protein subunit alpha transducin 1 Retina Positivity in rod segments.
GNGT1 G protein subunit gamma transducin 1 Retina Positivity in rods.
GNGT2 G protein subunit gamma transducin 2 Retina Positivity in cones.
GRK1 G protein-coupled receptor kinase 1 Retina Positivity in photoreceptor cells.
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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