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Stem Cells are a Potential Therapy for Age-related Macular Degeneration
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Stem Cells are a Potential Therapy for Age-related Macular Degeneration

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Highlights:
  • The presence of primary cilia on the retinal pigment epithelium appears to be essential for the cells to be structurally and functionally mature
  • Stem cells treated with cilia-promoting drugs were structurally and functionally mature, and formed a monolayer
  • Mutations in the cilia-promoting genes resulted in defective retinal pigment epithelial cells

In a paper published in Cell Reports, scientists reiterated the importance of primary cilia on retinal epithelial cells to make them structurally and functionally mature and support the photoreceptors of the eye.

The retinal pigment epithelial cells (RPE) are special cells that support and nourish the photoreceptors in the inner layer of the eye. The mature cells have thread-like structures called primary cilia, which appear to be important for their function. The cilia suppress the canonical WNT pathway, thereby signaling to the cells to stop dividing and being maturing. The RPE cells are affected by geographic atrophy or dry age-related macular degeneration (AMD); this is followed by a gradual loss of vision due to the secondary effect on the photoreceptors.

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The scientists emphasized the importance of the cilia in the development of functional RPEs by exposing induced pluripotent stem cells (iPSC) programmed to form RPEs to two cilia promoting (aphidicolin and prostaglandin E2) drugs and one cilia-inhibiting (HPI-4) drug. The iPSC are stem cells that can be coaxed to develop into any type of cells.

On exposure of the cells to cilia-promoting drugs:
  • The RPE cells formed were structurally mature and were oriented as a single functional monolayer
  • Their genetic constitution resembled more of adult RPE cells
  • They engulfed the photoreceptor outer segments, which reflects the proper functioning of the RPE cells
  • Their cilia appeared to enhance the maturation of the cells by inhibiting the canonical WNT signaling. However, the suppression of the WNT signaling is not enough for the maturation of the RPEs, as demonstrated by further experiments and requires further PKCδ activation
When the cells were exposed to the cilia-inhibiting drug:
  • The RPE cells were immature structurally and functionally
When the genes responsible for the development of the cilia-protein IFT88 were knocked off:
  • The RPE cell density and the polarity of the cells were altered, resulting in maturational and functional defects
To confirm the results of their experiments, the scientists carried out their experiments in cells from patients as well as mice with ciliopathies, conditions with defective primary cilium function. Patients with ciliopathies develop retinal degeneration.
  • RPE cells from stem cells of patients with mutations in the cilia gene CEP290 had smaller cilia, with the resultant cells developing structural and functional defects. The lack of maturation of these cells was shown to be associated with retinal degeneration
  • The study in mice demonstrated that damage to the RPE cells occurs before the damage to the photoreceptors. It also emphasized the importance of WNT suppression to ensure the maturation of the RPE cells
A similar functional benefit of ciliated cells on the maturation of epithelial cells was noted in the lungs.

About Dry Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a condition where the photoreceptors (light-sensitive cells) in the macula undergo degeneration, usually above the age of 50 years, resulting in blurred vision. A family history and smoking increase the risk of developing the condition. In dry age-related macular degeneration, the photoreceptors as well as the supporting tissue in the macula consisting of retinal pigment epithelial cells undergo degeneration. There is no specific treatment for the condition. Some patients may benefit from the intake of mineral and vitamin supplements. In the recent years, treatment with stem cells is being explored for the condition. However, this approach has faced some roadblocks due to the incomplete maturation of the stem cells during the studies.

About the Retina

The retina is the inner light-sensitive layer of the eye. It detects the rays of light that enter the eye and converts them into electrical signals that are carried to the brain via the optic nerve. The retina contains two types of photoreceptors, the rods that detect dim light, and the cones that are responsible for colored vision. The macula is the most light-sensitive region with a maximum concentration of cones and is responsible for central vision.
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References :
  1. May-Simera, Helen Louise et al. "Primary Cilium Mediated Retinal Pigment Epithelium Maturation is Retarded in Ciliopathy Patient Cells". Cell Reports. Published online January 2, 2018. DOI:10.1016/j.celrep.2017.12.038
  2. Facts About Age-Related Macular Degeneration - (https://nei.nih.gov/health/maculardegen/armd_facts)
Source: Medindia

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