At Seinda, we investigate molecular mechanisms of different ophthalmic disorders by integrating
immunology, omics technology, and systems biology. This approach forms the bedrock of our
biomarker research, in vitro diagnostics and new drug development for ocular diseases. We
aim to
provide innovative solutions for more precise and effective patient care.
Immune Regulation of the Eye
The eye is continuously exposed to environmental agents such as allergens, pollutants,
and
microorganisms, which can provoke inflammation. Thus, a sufficient immune response
protects
the
eye from infection. However, a transparent cornea is vital for clear vision of the eye,
and
excessive inflammation of the eye can cause immune-mediated damage to the eye and
opaqueness
of
the cornea, clouding sight.
The ocular surface, as a unique mucosal immune compartment, has anatomical,
physiological, and immunological features act in combination to create and maintain an
immune-tolerant microenvironment, which is essential for maintaining normal vision and
healthy eyes. Some of the major components fostering the unique immune physiology found
at the ocular surface are the tear film, corneal epithelial cells, immune cells, and
many soluble immunoregulatory factors.
Ocular Immune Homeostasis
At mucosal surfaces like the ocular surface, the immune system at a
physiological state or homeostatic state does not initiate inflammatory immune
responses to self-tissues, commensal microbial antigens, or the plethora of antigens
constantly present in the environment. In this state, it remains poised to unleash a
potent assault on invading pathogens and to respond to environmental insults. Thus,
it is necessary for resident immune cells to switch from the homeostatic (often
tissue-protective) state to a potent antimicrobial immunity or inflammatory state
during local inflammatory process and tissue injury, followed by resolution of acute
inflammation, clearance of pathogen and apoptotic cells, wound healing, tissue
repair, and restoration of a homeostatic state. Disruption of this delicate balance
of the immune system (i.e. loss of immune homeostasis) can lead to the development
of ocular surface disorders.
Tear Film and Ocular Health
Tear film is the liquid layer that coats the outer surface of the eye, forming a
protective film by lubricating it. The tear film consists of lacrimal fluid and the
secretion of the meibomian and conjunctival glands of the eye. The tear film is
typically viewed as composing of three layers:
1.The outer lipid (oily) layer, produced by the meibomian glands;
2.The middle aqueous (watery) layer forming the bulk of the tear film, produced
by the main and accessory lacrimal glands, and containing most of the
bactericidal lysosyme and other proteins, inorganic salts, sugars, amino acids,
urea, etc.; and
3.The inner hydrophilic mucin layer, produced by the conjunctival goblet cells
and making up the
deepest and densest layer.
The tear film prevents dehydration of the mucosal surface, provides protection against
pathogens and nutrition for the underlying corneal and conjunctiva epithelial cells, and
maintains the well-being of the corneal and conjunctival epithelium. The tears contain
thousands of molecules including proteins, peptides, lipids, electrolytes, small molecule
metabolites, and water. They come from the main and accessory lacrimal glands, meibomian
glands, goblet cells, and ocular surface epithelial cells.
Goblet cells (GCs) are cells that secrete gel-forming mucins and are widely distributed
throughout mammalian mucosal surfaces, including the conjunctiva. On the ocular surface, GCs
are principal mucin-secreting cells in the conjunctival epithelia. Mucins lubricate the
ocular surface epithelia during blinking, stabilize the tear film, and act as a physical
barrier to external pathogen and particles. Loss of GCs and alteration in GC function
diminishes mucin secretion in the ocular surface, which is associated with unstable tear
film and vulnerable ocular surface. Loss of GCs and depletion of mucin in tear film have
been reported in dry eye.
Tear film plays a key role in regulating ocular immune homeostasis. Any abnormal composition
or production of tear film can destabilize it, which may disturb the balance of the ocular
immune system and lead to loss of homeostasis. Thus, analysis of tear film is valuable for
the assessment of pathological changes and immune homeostasis in the ocular surface.
Tear Biomarker Analysis
A specific disease biomarker is defined as a measurable characteristic in a biological
system which changes due to disease, exposure to chemicals or other factors. Tears
contain 1800~2000 of proteins and peptides, other ocular matrices (e.g. aqueous humor
and vitreous) also contain proteins and peptides. Physiological and pathological changes
in the ocular surface are reflected in the tear composition and can be uncovered through
biomarker analysis. Tear composition contains information of the pathophysiology of the
ocular surface. Thus, by measuring the amounts and changes of different protein factors
of various signal transaction pathways in tear samples, we can identify associations
between molecular pathways and the pathophysiological mechanisms of diseases.
Through tear biomarker analysis, along with systems biology and bioinformatics for data
analysis and mining, we delineate underlying signal transaction pathways and identify
biomarkers of different ocular conditions.
In Vitro Diagnostics
New Drug Therapies
Through tear biomarker analysis, we are able to identify specific biomarkers for
different ophthalmic diseases based on their molecular mechanisms to facilitate
diagnosis. Moreover, this information may help stratify patients into
subgroups. Relying on this research, we are able to develop rapid POC in
vitro
diagnostics that offer quantitative,
repeatable, and precise results. Learn more about our POC in vitro
diagnostic
platform at i-ImmunDxTM Platform and POCT
Products.
By identifying the specific molecular mechanisms of different diseases, we are
better equipped to create targeted therapies that address the underlying causes of
ocular disorders. Targeted drug therapy is one of the most promising methods for
effective treatment because of its ability to improve the efficacy of the treatment
while reducing side effects. Learn more about our new drug candidates in development
at Therapeutics.
