Transplant registers

Team members are currently building a database in order to analyze the functional results of corneal transplants. The clinical and immunological phenomena of tissue compatibility will be closely studied.
A histological section of rabbit cornea in which the anterior epithelium can be observed. This layer of cells is bathed by tears and acts as a barrier against infection. The medial aspect (stroma) represent 90% of the cornea’s width. It is made of collagen and other conjunctive tissues. The posterior aspect is made of a single layer of cells named corneal endothelium. Corneal endothelium is responsible for the continued transparency of the cornea.

The eye’s immunology is quite particular and very different from the rest of the body; consequently the graft rejection rate is much lower than in other transplants. In spite of this, 20% of all transplanted cornea will go through some type of rejection process after three years. The cornea is still subject to immune reactions even if the vascularization of the corneal tissue is quite low. This research project aims to lower the rejection rate in corneal transplants.



This image of corneal endothelium
from a human subject was obtained from
a specular miscroscope.
Most cells have
a hexagonal
shape that
is relatively regular.
This is an
image of corneal endothelium
from a human subject suffering from cornea guttata. Again
the image was obtained
with a specular microscope.The endothelium
of this patient presents
abnormal dark spots, the guttae, which is known
to be a predisposition
from Fuch’s dystrophy. This progressive condition
is a frequent
cause of corneal transplants in
order to replace the
malfunctioning endothelium
with that
of the deceased donor.

Scarring of corneal lesions

Team members are also studying the role played by integrins a4b1 and a5b1 in the scarring process of in-vitro reconstructed cornea. Since the cornea is not vascularized, the scarring process following a transplant is somewhat complex and longer than for other surgeries performed on the eye. From this stems the need to understand the underlying scarring mechanisms, more so now that more corneal surgeries are done with lasers where the scarring process can sometimes cause more damage than the surgery itself. We must favor healing without scarring.



Macroscopic photograph of a human cornea recreated in vitro.

Another important part of this team’s research centers on developing tissue genetics in order to recreate the human cornea. This recreated cornea will then be used as in-vitro models and eventually transplanted in patients with severe eye burns. Team members are also developing a permeable fiber that will be used as a support structure for cultured endothelium cells. This model will help study the processes that help maintain corneal transparency, essential for clear vision.

 

Creation and management of
a clinical and molecular database

Open-angle glaucoma is a disease with a hetero-geneous genetic component. In the province of Quebec, these deleterious genes are responsible for at least 30%, if not 50 %, of reported cases of open-angle glaucoma. To understand the molecular causes of open-angle glaucoma, team members are using positional cloning and the gene candidate approach to map and identify the genes responsible for open-angle glaucoma. From molecular epidemiological studies they will trace the type and frequency of the most common genetic mutations in Quebec, their individual contribution to the sporadic cases of glaucoma that arise and the way these mutations penetrate families.

The answers to theses questions will be found in our database containing clinical and molecular information on all types of glaucoma occurring in Quebec. Clinical data will be included in our database in order to determine the phenotypes associated with the different mutations of the disease in Quebec. This infrastructure will allow us to give quick molecular diagnostics to clinicians so that they can treat the disease before it becomes symptomatic, hence preventing blindness.

Development of new prognostic indicators

The current prognostic tests that allow us to determine the long term effects of glaucoma and measure treatment results are not very reliable, nor easily reproducible. With the help of neurovascular imagery, the glaucoma axis team members are studying the possibility of using changes to the structure of the head of the optic nerve, changes in blood flow in the optic nerve and neighboring zones and changes to the thickness of the layers of nervous fibers as prognostic indicators.

In order to do this, researchers are using scanning Doppler laser fluxmetry, retinal tomography, and scanning laser polarimetry. Other than measuring absolute changes in neuronal structure and blood flow, ocular hemodynamics are studied during test aimed at evaluating the integrity of vascular autoregulation.

Surgery and scarring

The treatments (medication, laser and surgery) do not heal chronic glaucoma; they control its evolution in order to prevent future damage. When neither medication or lasers can control the interocular pressure, then surgical procedures are used. The intervention consist of a one millimeter drain in the eye that allows liquid to exit. However, in over half of patients this drain closes naturally within five years. Hence, researchers must find a way to prevent this phenomenon.

In order to stop this phenomenon, some forms of medication are administered, such as anti-scarring, anti-fibrotic, and even anti-carcinogens. In vitro studies are being conducted to determine the effects of anti-scarring medication, particularly mitomycine which is frequently used after a trabeculectomy. A comparison of surgical results obtained with patients (Tenon’s biopsy during a trabulectomy) will permit researchers to establish if there is a correlation between results found in vitro and surgical results ( i.e. to determine the efficacy of the treatment).