The Royal College of Surgeons rat: an animal model for inherited retinal degeneration with a still unknown genetic defect.
The Royal College of Surgeons (RCS) rat is the first known animal with inherited retinal degeneration. Despite the fact that the genetic defect is not known, the RCS rat is widely used for research in hereditary retinal dystrophies. This review tries to summarize observations which have been made in the RCS rat and to make an attempt to formulate candidate genes which may the cause for the retinal degeneration in this rat strain. The genetic defect in RCS rats causes the inability of the retinal pigment epithelium (RPE) to phagocytose shed photoreceptor outer segments. In normal rats or humans, this circadian process is regulated by both the cyclic adenosine monophosphate (cAMP) and the calcium/ inositol phosphate systems. The calcium/inositol phosphate system seems to be linked to the phagocytosis receptors which recognize photoreceptor outer membranes to initialize phagocytosis. The cAMP system appeared as modulator of the regulation of phagocytosis. An increase in the intracellular cAMP concentration is an 'off' signal for phagocytosis. In RPE cells from RCS rats many observations have been made which indicate a changed second messenger metabolism concerning both the cAMP and the calcium/inositol phosphate systems. The genetic defect seems to concern a protein which is involved in the initialization of a second messenger pathway. We conclude that the genes coding for the phagocytosis receptor or for proteins which are linked to receptors (for example G proteins) are good candidates for defective genes in RCS rats.
Strauss
O
O
Institut für Klinische Physiologie, Universitätsklinikum Benjamin Franklin der Freien Universität Berlin, Deutschland. strauss@ukfb.fu-berlin.de
Stumpff
F
F
Mergler
S
S
Wienrich
M
M
Wiederholt
M
M
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D010587:Phagocytosis / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D015290:Second Messenger Systems / Q000502:physiology