Institute of Clinical Physiology

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Dept. Gastroenterology
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Physiology of the Eye
Research topics

Researcher:   Rita Rosenthal
Cooperation:  Olaf Strauss, Experimental ophthalmology, Charité
                     Hagen Thieme, Ophthalmology, Mainz
                    

  eye Topics  

We focused on studying the physiology and pathophysiology of various ocular tissues known to malfunction in diseases of the eye. One major topic is glaucoma, where efforts concentrate on the tissues involved in outflow regulation (trabecular meshwork, ciliary muscle and scleral spur). A second main point of interest concerns the study of retinal pigmented epithelium, a tissue involved in various forms of hereditary retinal degeneration.

Glaucoma: Elevated intraocular pressure results in loss of visual function, ultimately leading to blindness. Impaired outflow of aqueous humor through the trabecular meshwork is believed to be one of the factors contributing to glaucoma. Research in this laboratory has demonstrated that trabecular meshwork has contractile properties, is actively involved in outflow regulation, and is therefore a potential target tissue for glaucoma therapy. One of our current concerns is to study the relative contractile response of trabecular meshwork and ciliary muscle in response to various pharmacological agents. In addition, cultured bovine and human trabecular meshwork, ciliary muscle, and scleral spur cells form the basis for patch clamp and molecular biology studies with the goal of elucidating signal transduction pathways linked to contractile response.

Retinal degeneration: The retinal pigmented epithelial cells envelope the outer segments of the light-sensitive photoreceptors, thus enabling them to function and interact with each other. Breakdown of this interactions leads to loss of photoreceptor function and ultimately to retinal degeneration. Currently, retinal dystrophies are being investigated in rat and mouse animal models of retinitis pigmentosa* as well as Norrie's disease. The focus lies in the secretory function of the retinal pigmented epithelium, because there is evidence to suggest that altered growth factor secretion might play an important role in retinal degeneration.

In addition, this altered secretion of growth factors by retinal pigment epithelial cells can be considered as the main cause for the induction of choroidal neovascularization in age-related macular degeneration. In cooperation with the eye hospital we are investigating the underlying mechanisms by studying cells from neovascular membranes which have been isolated by eye surgery of patients with age-related macular degeneration.

Ionic channels and their interaction with regulatory proteins are being investigated with patch-clamp techniques and molecular biological approaches. The interaction of ionic channels with tyrosine kinases is one of the main research topics.

*For excellent and detailed information on retinitis pigmentosa visit the International Retinitis Pigmentosa Association (IRPA) or the Pro Retina Deutschland e.V. (in German).

  eye Methods eye 

Cell culture techniques: Rat, bovine and human cell cultures (trabecular meshwork, ciliary muscle, scleral spur and retinal pigmented epithelial cells).

Contractility measurements: The contractile force of prepared bovine trabecular meshwork and ciliary muscle strips is measured using a force length transducer system. The response of the strips in response to various pharmacological agents is studied.

Patch-clamp technique: Our interest concerns both characterization of ion channels as well as clarifying signal transduction pathways. Whole cell, perforated patch, and single channel techniques are applied. Calcium, potassium, chloride and sodium channels have been studied in retinal pigmented epithelium, trabecular meshwork, ciliary muscle, or scleral spur.

Intracellular calcium measurements: FURA-2 acts as a calcium sensitive dye and enables direct calcium measurements in living cells. The measurements are performed simultaneously with patch-clamp recordings.

Molecular biology: Cell cultures are investigated by protein blotting methods (Western blotting, immunoprecipitation). The main focus lies on signal transduction proteins, receptors, enzymes and their regulation. In addition, PCR-techniques have been established.