Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal

Monica Jablonski, J. Tombran-Tink, D. A. Mrazek, A. Iannaccone

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Dysfunction of the retinal pigment epithelium (RPE), its loss, or separation from the underlying neural retina results in severe photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a glycoprotein with reported neuroprotective and differentiation properties that is secreted in abundance by RPE cells. The 'pooling' of PEDF within the interphotoreceptor matrix places this molecule in a prime physical location to affect the underlying neural retina. The purpose of this study was to analyze the morphogenetic activity of PEDF in a model of photoreceptor dysmorphogenesis induced by removal of the RPE. Eyes were dissected from embryonic Xenopus laevis, and the RPE was removed before culturing in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone. Control retinas were maintained with an adherent RPE. Light and electron microscopic analysis was used to examine retinal ultrastructure. Opsin was localized immunocytochemically and quantified as an index of outer segment membranous material and photoreceptor protein expression. Removal of the RPE resulted in an aberrant assembly of photoreceptor outer segments, loss of fine subcellular ultrastructure in photoreceptors, and a reduction in opsin protein levels when compared with control retinas. The addition of PEDF prevented the dysmorphic photoreceptor changes induced by RPE removal. In particular, photoreceptor ultrastructure, outer segment membrane assembly, and steady-state levels of opsin were equivalent to control conditions. Anti-PEDF antibodies completely blocked the morphogenetic activity of PEDF. These results indicate that PEDF is able to mimic the supportive role of the RPE on photoreceptors during the final stages of retinal morphogenesis.

Original languageEnglish (US)
Pages (from-to)7149-7157
Number of pages9
JournalJournal of Neuroscience
Volume20
Issue number19
StatePublished - Oct 1 2000

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Opsins
Retinal Pigment Epithelium
Neurons
Retina
pigment epithelium-derived factor
Antibodies
Xenopus laevis
Morphogenesis
Glycoproteins
Proteins
Electrons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal. / Jablonski, Monica; Tombran-Tink, J.; Mrazek, D. A.; Iannaccone, A.

In: Journal of Neuroscience, Vol. 20, No. 19, 01.10.2000, p. 7149-7157.

Research output: Contribution to journalArticle

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