Greferath Lab ~ Current Projects

1. Imaging visual processing

Visual processing begins in the retina. Here, the contrast, color, shape, and movement of an object are analyzed and processed in discrete circuits and pathways. We are interested in how cells in the retina react to visual stimulation and furthermore how they ‘talk’ to each other. To study this, we utilize a transgenic mouse, which enables us to label and see active retinal cells, and to trace their processes and connections to the other cells they talk to. This mouse the fos-tau-LacZ (FTL) uses the c-fos promoter to drive the expression of a marker protein beta-galactosidase specifically into neuronal processes. Only neurons in the retina which are functionally activated by a visual stimulus express c-fos and thus are b-galactosidase positive.

Light activated b-galactosidase positive neurons in the FTL retina visualised by immunoflourescence in a cross-section (left) and in a retinal flat-mount, which was stained for b-galactosidase histochemistry (right).

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2. The role of histamine in visual processing

The vertebrate retina not only projects to the visual areas of the brain, but it also receives input from the brain via retinopetal projections. One of these projections originates in the posterior hypothalamus and contains the neurotransmitter histamine. The function of these interesting brain derived projection is unknown but it might convey some form of modulation of optic output. In an attempt to study and understand the function of histamine in the retina, we are labeling the histaminergic axons coming from the brain and localize histamine receptors (HR1,2,3) in the mouse retina with immuno fluorescence.

Histaminergic retinopetal axons in the flatmount of mouse retina stained with an antibody specific to histamine and immunoflourescence.

3. Functional consequences of photoreceptor death in retinal degeneration

Age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa cause progressive blindness due to loss photoreceptors in the retina. Following photoreceptor loss, remaining retinal circuits can undergo significant alterations, which will further impede normal retinal function. We are interested in fully understanding the effect of these diseases on the entire retina, which is an essential requirement for current and future restorative therapies to be effective. By using an experimental mouse model, genetically modified to both carry a gene for retinitis pigmentosa (rd/rd), and to allow visualisation of light activated circuits in the retina (FTL, see above), we are studying retinal function and the consequences of photoreceptor loss.

Rod photoreceptor in the retina of a Rd-FTL mouse expressing b-galactosidase (green fluorescence) prior to degeneration.