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Vitronectin Gene Expression in the Adult Human Retina

¹ From the Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara; ² The University of Iowa Center for Macular Degeneration, Iowa City; ³ Department of Cell Biology and Anatomy and ⁴ The Eye Institute, Medical College of Wisconsin, Milwaukee; ⁵ Institut fur Biochemie, Justus-Liebig-Universitat, Giessen, Germany.

PURPOSE. To determine whether vitronectin (Vn), a plasma protein and extracellular matrix molecule that is also a prominent constituent of drusen, is synthesized by cells in the adult human retina.

METHODS. The distribution of Vn in the normal adult human retina was examined using antibodies to circulating plasma Vn and to the multimeric, heparin-binding form that is most prevalent in extravascular tissues. Evidence of Vn transcription by retinal cells was analyzed by in situ hybridization and also by reverse transcription of total RNA derived from dissociated human or mouse photoreceptors followed by amplification using polymerase chain reaction (RT-PCR).

RESULTS. Cytoplasmic immunoreactivity for plasma Vn or multimeric Vn was detected in photoreceptors, in a subpopulation of neurons situated in the inner retina, and in vitreous hyalocytes. Extracellular labeling was limited primarily to Bruch’s membrane and the retinal vasculature. At the transcriptional level, Vn mRNA was localized to both photoreceptors and ganglion cells by in situ hybridization. The in situ findings were corroborated by RT-PCR using total RNA from dissociated mouse or human photoreceptor cells.

CONCLUSIONS. The results constitute the first evidence for Vn gene expression by adult neurons in the mammalian central nervous system. The identification of the photoreceptors as a cellular source of Vn suggests that these cells have the potential to make a biosynthetic contribution to the Vn that is found in drusen.

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