• Retinopathy of prematurity
• Identification of the genes and proteins responsible for retinal disease
• Electro diagnostic evaluations
• Malignant eye tumor register
• Development of diagnostic tools
• Cytokines in the non-infectious uveitis

Retinopathy of prematurity

To increase their chance of survival, premature infants are often treated with excessively high concentrations of oxygen. Unfortunately, these high concentrations of oxygen can seriously damage the retina. Retinopathy of prematuratity is, without a doubt, the most serious problem that these infants face. Though we well understand the main cause of retinopathy of prematurity (high concentrations of oxygen), we have yet to understand the physiopathalogical process that leads to the expression of the disease. Between 40 and 60 % of premature infants (<1000 gr. at birth and/or < 29 weeks) will develop retinopathy of prematurity, 25 to 40 % of these infants will be afflicted with serious problems such as strabism, amblyphobia, severe myopia and trouble perceiving chromatic stimuli. In the most severe cases, blindness may occur as a result of retinal detachment.

Blood flow to the retina depends on blood vessels within it and in the choroids both of which supply nutrients and oxygen to the retina. The retina’s vascular network develops between the 23rd week and 40th week of gestation. Vascularisation of the retina is incomplete and fragile to extra-uterine oxygen in infants born before the 29th week of gestation.

Research by team members on some of the compounds responsible for the harmful effects of oxygen on the vascularisation of the retina, amongst them isoprostane and thromboxane, has led to the effective use of inhibitors to delay the progression of retinopathy of the premature. However, the underlying mechanisms responsible for the harm caused by these compounds are still misunderstood. Current research aims for a better understanding of the mechanisms of these compounds in order to shield premature infants from retinopathy of the premature.

Identification of the genes and
proteins responsible for retinal disease

The pigmented retinal epithelium (PRE) is essentiel for normal visual function, among other things it allows the phagocytosis of photoreceptors and their intake of nutrients and metabolites. Research has shown that a malfunction of the PRE, such as a very low phagocytosis rate, can lead to the degeneration of photoreceptors.

< Illustration
of a model that proposes that there is an interaction between
excessive O2, reactive species
of O2 (ROS), isoprostanes and thromboxane (TXA2) in vasoconstriction and vasoliberation in the immature retina. The interaction predisposes the premature retina to neovascu-larisation and retinal
dysfunction.

A problem in digesting lipids from the photoreceptors may be responsible for the abnormal accumulation of lipids, particularly in the basal portion of the PRE, found in aged subjects afflicted with macular degeneration. It is possible that these accumulations are the result of an enzymatic malfunction in the degradation of phagosomes, such as phospholipases A2 that have recently been cloned by team members. Research is also underway to determine if mutations exist in genes expressed by the retina’s Muller cells in subjects afflicted with diabetic retinopathy. Moreover, researchers are also searching for other genes specifically expressed by Müller cells in the retina of patients suffering from diabetic retinopathy in order to determine if a mutation exist in these genes.

Electro diagnostic evaluations

Different retinal pathologies, both genetic and acquired (for example, ischaemic disorders such as retinopathy of the premature), affect the way neurons in the retina and the brain work. Research by experts in the field of visual electrophysiology has allowed us to indentify the mechanisms involved in retinal dysfunction. It has been shown that different types of retinitis pigmentosa elicit different electrical responses during an electroretinography. Adding an electroretinography to the traditional clinical exam allows for an early and accurate diagnosis and leads us to a better understanding of the evolution of the disease.

< Lipidic deposits between the PRE and the choroids provoke a deficiency in
the lysosomal enzymatic machinery that causes the degeneration
of the photo-receptors.

< Fundus photographs show a normal posterior pole (left) with RPE mottling and few bone spicules seen in the supero-nasal quadrant of the right eye (right).

>As predicted
from fundus photographs,
the visual field
(left eye shown) indicates a
supero-temporal ring scotoma. Areas of blindness (scotoma) are shown in dark.
A similar picture but with less field defect was noted in the right eye.

Cone (column A) and rod (column B) electroretinograms recorded from a normal subject (tracings 1: A and B) and from our RP patient (tracings 2: A and B). Typically, in the early stage of retinitis pigmentosa, the electroretinogram will show a severely depressed rod response (column B, tracing 2) while the cone response will be less affected (column A, tracing 2). With progression of the disease, both responses can become extinguished. S indicates stimulus (flash of light) onset.

Electroretinography tests are also used to compare the way the visual pathways of normal subjects, amblyopic subjects and subjects suffering from traumatic cerebral damage process visual information. In fact, team members combine evoked visual potentials with a psychophysical measure, reaction time, in order to further our knowledge of the magnocellular and parvocellular systems of the visual brain, which respectively allow perception of movement and shape.