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Attainment of polarity promotes growth factor secretion by retinal pigment epithelial cells: relevance to age-related macular degeneration.

Sonoda S, Sreekumar PG, Kase S, Spee C, Ryan SJ, Kannan R, Hinton DR - Aging (Albany NY) (2009)

Bottom Line: PEDF secretion was about 1000 fold greater than that for VEGF in both polarized and non-polarized cultures.Treatment of non-polarized RPE cultures with bone morphogenetic protein-4 (BMP-4) had no effect on PEDF or VEGF secretion, but resulted in a dose-dependent >2-fold increase in basolateral VEGF secretion (p<0.05) in polarized cultures.Our data show that polarity is an important determinant of the level of PEDF and VEGF secretion in RPE and support the contention that loss of polarity of RPE in AMD results in marked loss of neurotrophic and vascular support for the retina potentially leading to photoreceptor loss and blindness.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.

ABSTRACT
The antiangiogenic and neurotrophic growth factor, pigment epithelial derived factor (PEDF), and the proangiogenic growth factor, vascular endothelial growth factor-A (VEGF), are released from retinal pigment epithelial (RPE) cells where they play a critical role in the pathogenesis of age-related macular degeneration (AMD). Since RPE polarity may be altered in advanced AMD, we studied the effect of polarization of differentiated, human RPE monolayer cultures on expression and secretion of PEDF and VEGF. Polarized RPE demonstrated apical microvilli, expression of tight junction proteins, apical localization of Na/K- ATPase, and high transepithelial resistance (490 +/- 17 Omega x cm(2)). PEDF secretion was about 1000 fold greater than that for VEGF in both polarized and non-polarized cultures. Polarization of the RPE monolayer increased PEDF secretion, which was predominantly apical, by 34 fold (p<0.02) and VEGF secretion, which was predominantly basolateral, by 5.7 fold (p<0.02). Treatment of non-polarized RPE cultures with bone morphogenetic protein-4 (BMP-4) had no effect on PEDF or VEGF secretion, but resulted in a dose-dependent >2-fold increase in basolateral VEGF secretion (p<0.05) in polarized cultures. Our data show that polarity is an important determinant of the level of PEDF and VEGF secretion in RPE and support the contention that loss of polarity of RPE in AMD results in marked loss of neurotrophic and vascular support for the retina potentially leading to photoreceptor loss and blindness.

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Effect of rhBMP-4 treatment on secretion of VEGF-A and PEDF from nonpolarized RPE cells. Secretion of VEGF-A (A)                                        and PEDF (C) are presented along with the corresponding cellular                                        VEGF-A (B) and cellular PEDF (D) from three different donors.                                        Data are presented as fold difference as compared to untreated controls. The cellular                                        concentrations of VEGF-A and PEDF did not differ from untreated controls                                        for the entire BMP-4 concentration range.
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Figure 7: Effect of rhBMP-4 treatment on secretion of VEGF-A and PEDF from nonpolarized RPE cells. Secretion of VEGF-A (A) and PEDF (C) are presented along with the corresponding cellular VEGF-A (B) and cellular PEDF (D) from three different donors. Data are presented as fold difference as compared to untreated controls. The cellular concentrations of VEGF-A and PEDF did not differ from untreated controls for the entire BMP-4 concentration range.

Mentions: The effect of rhBMP-4 (24 hrs; 10-100 ng/ml) on the secretion of VEGF-A and PEDF from non-polarized, confluent human RPE cells was determined in RPE isolated from three individual donors. No significant change in VEGF or PEDF secretion or cellular protein expression was found in non-polarized RPE after treatment with BMP-4 at any of the tested doses (Figure 7).


Attainment of polarity promotes growth factor secretion by retinal pigment epithelial cells: relevance to age-related macular degeneration.

Sonoda S, Sreekumar PG, Kase S, Spee C, Ryan SJ, Kannan R, Hinton DR - Aging (Albany NY) (2009)

Effect of rhBMP-4 treatment on secretion of VEGF-A and PEDF from nonpolarized RPE cells. Secretion of VEGF-A (A)                                        and PEDF (C) are presented along with the corresponding cellular                                        VEGF-A (B) and cellular PEDF (D) from three different donors.                                        Data are presented as fold difference as compared to untreated controls. The cellular                                        concentrations of VEGF-A and PEDF did not differ from untreated controls                                        for the entire BMP-4 concentration range.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837203&req=5

Figure 7: Effect of rhBMP-4 treatment on secretion of VEGF-A and PEDF from nonpolarized RPE cells. Secretion of VEGF-A (A) and PEDF (C) are presented along with the corresponding cellular VEGF-A (B) and cellular PEDF (D) from three different donors. Data are presented as fold difference as compared to untreated controls. The cellular concentrations of VEGF-A and PEDF did not differ from untreated controls for the entire BMP-4 concentration range.
Mentions: The effect of rhBMP-4 (24 hrs; 10-100 ng/ml) on the secretion of VEGF-A and PEDF from non-polarized, confluent human RPE cells was determined in RPE isolated from three individual donors. No significant change in VEGF or PEDF secretion or cellular protein expression was found in non-polarized RPE after treatment with BMP-4 at any of the tested doses (Figure 7).

Bottom Line: PEDF secretion was about 1000 fold greater than that for VEGF in both polarized and non-polarized cultures.Treatment of non-polarized RPE cultures with bone morphogenetic protein-4 (BMP-4) had no effect on PEDF or VEGF secretion, but resulted in a dose-dependent >2-fold increase in basolateral VEGF secretion (p<0.05) in polarized cultures.Our data show that polarity is an important determinant of the level of PEDF and VEGF secretion in RPE and support the contention that loss of polarity of RPE in AMD results in marked loss of neurotrophic and vascular support for the retina potentially leading to photoreceptor loss and blindness.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.

ABSTRACT
The antiangiogenic and neurotrophic growth factor, pigment epithelial derived factor (PEDF), and the proangiogenic growth factor, vascular endothelial growth factor-A (VEGF), are released from retinal pigment epithelial (RPE) cells where they play a critical role in the pathogenesis of age-related macular degeneration (AMD). Since RPE polarity may be altered in advanced AMD, we studied the effect of polarization of differentiated, human RPE monolayer cultures on expression and secretion of PEDF and VEGF. Polarized RPE demonstrated apical microvilli, expression of tight junction proteins, apical localization of Na/K- ATPase, and high transepithelial resistance (490 +/- 17 Omega x cm(2)). PEDF secretion was about 1000 fold greater than that for VEGF in both polarized and non-polarized cultures. Polarization of the RPE monolayer increased PEDF secretion, which was predominantly apical, by 34 fold (p<0.02) and VEGF secretion, which was predominantly basolateral, by 5.7 fold (p<0.02). Treatment of non-polarized RPE cultures with bone morphogenetic protein-4 (BMP-4) had no effect on PEDF or VEGF secretion, but resulted in a dose-dependent >2-fold increase in basolateral VEGF secretion (p<0.05) in polarized cultures. Our data show that polarity is an important determinant of the level of PEDF and VEGF secretion in RPE and support the contention that loss of polarity of RPE in AMD results in marked loss of neurotrophic and vascular support for the retina potentially leading to photoreceptor loss and blindness.

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Related in: MedlinePlus