gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Genes expressed in RPE/choroid show a lower expression in the macula than in the periphery of normal human eyes

Meeting Abstract

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  • corresponding author N. Kociok - University Hospital of Cologne, Center of Ophthalmology, Department of Vitreoretinal Surgery, Cologne
  • B. Kirchhof - University Hospital of Cologne, Center of Ophthalmology, Department of Vitreoretinal Surgery, Cologne
  • A.M. Joussen - University Hospital of Cologne, Center of Ophthalmology, Department of Vitreoretinal Surgery, Cologne

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogP 215

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Veröffentlicht: 22. September 2004

© 2004 Kociok et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Retinal degeneration in AMD occurs predominantly in the macula whereas the peripheral retina virtually remains intact. It is thought that RPE and choroid are involved in this degeneration process. In addition, it is known that there is an increase of apoptosis of the RPE cells solely in the macula zone in the aging eye. Differences in gene expression of central versus peripheral RPE/choroid may be the cause for the differences in the cell faith. We therefore quantified the mRNA expression of genes in RPE/choroids that are important for their function and compared their expression in probes isolated from the macular area and the periphery of normal human donor eyes.

Methods

After removal of the anterior part and the vitreous of human donor eyes the posterior segment were radially dissected by four cuts. RPE/choroid squares of about 8mm2 were cut out and lysed in RNA lysis buffer. After RNA preparation and oligo-d(T) primed reverse transcription the analyzed genes were quantified by SybrGreen I -based Real Time RT-PCR. For normalizing the housekeeping gene GAPDH (glyceraldehyde-3-phosphate dehydrogenase) was used.

Results

The spatial mRNA expression in human RPE/choroid of 19 genes were analyzed. Normalization with the calibration gene GAPDH resulted in comparable mean normalized expression data. Genes important for rod outer segment phagocytosis (MERTK/Gas6, aVβ5-integrin receptor, CD36/scavanger receptor) showed a lower expression in the macula compared to the periphery. Genes involved in the retinoid metabolism (RPE65, 11-cis retinol dehydrogenase, Cathepsin D) as well as RPE-characterizing genes (tyrosinase) showed also a lower expression in the macula. Genes responsible for the integrity of the choriocapillaris (VEGF, PEDF, VEGF-R1 and R2) were differently expressed. Whereas VEGF and PEDF demonstrated a lower expression in the macula region both receptors showed no difference in their expression between macula and periphery. Genes for neurotrophic factors (BDNF, GDNF) were expressed in equal amount in the macula and periphery. From the apoptosis related genes the receptor FAS and his ligand Fas-L displayed also no expression differences between macula and periphery.

Conclusions

It is remarkable that there is a lower gene expression of important genes in the human RPE/choroid of the macula compared to the periphery. It is possible that macula specific constrains hinder a higher gene expression which occurs in the periphery. If this is so any additional pressure due to the aging process may overstrain the capacity of the RPE/choroid to maintain the physiological status of the macula in the aging eye. A further comparison in pathologically changed eyes (e.g. AMD) may elucidate whether an overall low gene expression in the macula contributes to the onset or progression of the degenerative retinal process or whether the influence of a specific gene activity is important.