Retinal pigment epithelial cell transplantation could provide trophic support in Parkinson's disease: Results from an in vitro model system

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Abstract

Transplantation of retinal pigment epithelial (RPE) cells in the basal ganglia could provide a novel cell-based therapy for Parkinson's disease by providing a constant source of dopamine replacement via the melanin synthetic pathway enzyme tyrosinase. We now demonstrate that human RPE cells also produce a neurotrophic effect on primary cultures of rat striatal (enkephalinergic) and mesencephalic (dopaminergic) neurons. Differentiation of RPE cells to a pigmented monolayer using a Ca++-switch protocol increased the potency of the neurotrophic effect on dopaminergic neurons. Conditioned medium derived from differentiated RPE cells increased neurite outgrowth in dopaminergic neurons by 125% compared to 25% for undifferentiated RPE cells. The neurotrophic effect was not due to tyrosinase activity. Differentiation of RPE cells doubled the production of pigment-derived epithelial factor (PEDF). However, PEDF accounted for only a portion of the neurotrophic effect as determined by depletion experiments and dose-response comparisons with purified PEDF, indicating that differentiation increased the production of other trophic factors as well. Conditioned medium from differentiated RPE cells also provided a neurotrophic effect on a subset of enkephalinergic striatal neurons increasing neurite outgrowth by 78%. Survival of enkephalinergic neurons in vitro was increased by RPE conditioned medium. In untreated cultures the number of enkephalinergic neurons declined 62% over a 2-week period compared to a 29% decline in RPE-treated cultures. These results indicate that transplantation RPE cells could potentially provide a dual benefit in Parkinson's disease producing both dopamine and neurotrophic support of the basal ganglia.

Original languageEnglish (US)
Pages (from-to)234-243
Number of pages10
JournalExperimental Neurology
Volume201
Issue number1
DOIs
StatePublished - Sep 2006

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Retinal Pigments
Cell Transplantation
Parkinson Disease
Epithelial Cells
Dopaminergic Neurons
Conditioned Culture Medium
Corpus Striatum
Monophenol Monooxygenase
Basal Ganglia
Neurons
Dopamine
Transplantation
In Vitro Techniques
Melanins
Cell- and Tissue-Based Therapy

Keywords

  • Cell transplantation
  • Dopaminergic neurons
  • Levodopa
  • Neurite length
  • Parkinson's disease
  • Pigment-epithelial derived factor
  • Retinal pigment epithelial cells
  • Striatal neurons
  • Trophic factors
  • Tyrosinase

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

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title = "Retinal pigment epithelial cell transplantation could provide trophic support in Parkinson's disease: Results from an in vitro model system",
abstract = "Transplantation of retinal pigment epithelial (RPE) cells in the basal ganglia could provide a novel cell-based therapy for Parkinson's disease by providing a constant source of dopamine replacement via the melanin synthetic pathway enzyme tyrosinase. We now demonstrate that human RPE cells also produce a neurotrophic effect on primary cultures of rat striatal (enkephalinergic) and mesencephalic (dopaminergic) neurons. Differentiation of RPE cells to a pigmented monolayer using a Ca++-switch protocol increased the potency of the neurotrophic effect on dopaminergic neurons. Conditioned medium derived from differentiated RPE cells increased neurite outgrowth in dopaminergic neurons by 125{\%} compared to 25{\%} for undifferentiated RPE cells. The neurotrophic effect was not due to tyrosinase activity. Differentiation of RPE cells doubled the production of pigment-derived epithelial factor (PEDF). However, PEDF accounted for only a portion of the neurotrophic effect as determined by depletion experiments and dose-response comparisons with purified PEDF, indicating that differentiation increased the production of other trophic factors as well. Conditioned medium from differentiated RPE cells also provided a neurotrophic effect on a subset of enkephalinergic striatal neurons increasing neurite outgrowth by 78{\%}. Survival of enkephalinergic neurons in vitro was increased by RPE conditioned medium. In untreated cultures the number of enkephalinergic neurons declined 62{\%} over a 2-week period compared to a 29{\%} decline in RPE-treated cultures. These results indicate that transplantation RPE cells could potentially provide a dual benefit in Parkinson's disease producing both dopamine and neurotrophic support of the basal ganglia.",
keywords = "Cell transplantation, Dopaminergic neurons, Levodopa, Neurite length, Parkinson's disease, Pigment-epithelial derived factor, Retinal pigment epithelial cells, Striatal neurons, Trophic factors, Tyrosinase",
author = "Mckay, {Brian S} and Brooke Goodman and Torsten Falk and Sherman, {Scott J}",
year = "2006",
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T1 - Retinal pigment epithelial cell transplantation could provide trophic support in Parkinson's disease

T2 - Results from an in vitro model system

AU - Mckay, Brian S

AU - Goodman, Brooke

AU - Falk, Torsten

AU - Sherman, Scott J

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N2 - Transplantation of retinal pigment epithelial (RPE) cells in the basal ganglia could provide a novel cell-based therapy for Parkinson's disease by providing a constant source of dopamine replacement via the melanin synthetic pathway enzyme tyrosinase. We now demonstrate that human RPE cells also produce a neurotrophic effect on primary cultures of rat striatal (enkephalinergic) and mesencephalic (dopaminergic) neurons. Differentiation of RPE cells to a pigmented monolayer using a Ca++-switch protocol increased the potency of the neurotrophic effect on dopaminergic neurons. Conditioned medium derived from differentiated RPE cells increased neurite outgrowth in dopaminergic neurons by 125% compared to 25% for undifferentiated RPE cells. The neurotrophic effect was not due to tyrosinase activity. Differentiation of RPE cells doubled the production of pigment-derived epithelial factor (PEDF). However, PEDF accounted for only a portion of the neurotrophic effect as determined by depletion experiments and dose-response comparisons with purified PEDF, indicating that differentiation increased the production of other trophic factors as well. Conditioned medium from differentiated RPE cells also provided a neurotrophic effect on a subset of enkephalinergic striatal neurons increasing neurite outgrowth by 78%. Survival of enkephalinergic neurons in vitro was increased by RPE conditioned medium. In untreated cultures the number of enkephalinergic neurons declined 62% over a 2-week period compared to a 29% decline in RPE-treated cultures. These results indicate that transplantation RPE cells could potentially provide a dual benefit in Parkinson's disease producing both dopamine and neurotrophic support of the basal ganglia.

AB - Transplantation of retinal pigment epithelial (RPE) cells in the basal ganglia could provide a novel cell-based therapy for Parkinson's disease by providing a constant source of dopamine replacement via the melanin synthetic pathway enzyme tyrosinase. We now demonstrate that human RPE cells also produce a neurotrophic effect on primary cultures of rat striatal (enkephalinergic) and mesencephalic (dopaminergic) neurons. Differentiation of RPE cells to a pigmented monolayer using a Ca++-switch protocol increased the potency of the neurotrophic effect on dopaminergic neurons. Conditioned medium derived from differentiated RPE cells increased neurite outgrowth in dopaminergic neurons by 125% compared to 25% for undifferentiated RPE cells. The neurotrophic effect was not due to tyrosinase activity. Differentiation of RPE cells doubled the production of pigment-derived epithelial factor (PEDF). However, PEDF accounted for only a portion of the neurotrophic effect as determined by depletion experiments and dose-response comparisons with purified PEDF, indicating that differentiation increased the production of other trophic factors as well. Conditioned medium from differentiated RPE cells also provided a neurotrophic effect on a subset of enkephalinergic striatal neurons increasing neurite outgrowth by 78%. Survival of enkephalinergic neurons in vitro was increased by RPE conditioned medium. In untreated cultures the number of enkephalinergic neurons declined 62% over a 2-week period compared to a 29% decline in RPE-treated cultures. These results indicate that transplantation RPE cells could potentially provide a dual benefit in Parkinson's disease producing both dopamine and neurotrophic support of the basal ganglia.

KW - Cell transplantation

KW - Dopaminergic neurons

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KW - Neurite length

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KW - Striatal neurons

KW - Trophic factors

KW - Tyrosinase

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