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.
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.
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.
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