In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-04-03)
Abstract:
The retina is the part at the back of our eyes that detects light and sends this information to our brain. Within the retina is a layered structure containing the light-sensitive cells, known as the neural retina, and another protective layer of cells called the retinal pigment epithelium. A surrounding network of blood vessels, the choroid, keeps the retina healthy by supplying oxygen and nutrients. When the choroid does not work properly, eye disease can result. A common example is age-related macular degeneration, where blood vessels in the choroid either break down or start growing uncontrollably in the wrong places. In both cases, light-sensitive cells are damaged and eventually die. This causes vision loss that worsens over time. The choroid forms early in life, within the developing embryo. The retinal pigment epithelium helps the choroid to develop properly by producing a protein, VEGF, which supports the growth of blood vessels. However, it was not clear what signals tell this tissue to start making VEGF in the first place and then to keep making it. To address this, Goto et al. looked at eye development in mutant mice that lack an enzyme called Aldh1a1. This enzyme’s role is to make a molecule called retinoic acid, which is known to be vital for many biological processes including the growth and development of embryos. Aldh1a1 is not made in the choroid of normal mice, just in the neural retina. Yet the choroid in the mutant mice without Aldh1a1 still grew fewer blood vessels than normal. Their retinal pigment epithelium also produced less VEGF and had lower levels of a protein called Sox9, which is known to make the gene for VEGF more active. Goto et al. went on to show that simply removing retinoic acid from the diet of normal mice produced the same choroid defect as in the mutant mice with no Aldh1a1. Genetically manipulating otherwise normal mice to decrease the levels of Sox9 in the retinal pigment epithelium had a similar effect. In contrast, giving Aldh1a1-deficient mice extra retinoic acid or artificially increasing their levels Sox9 was enough to make the choroid develop normally. These experiments showed that retinoic acid produced in the neural retina directs choroid development by making Sox9 more active, which in turn encourages the retinal pigment epithelium to produce VEGF. These findings bring new insights into the molecular signals that control choroid development. In the future, they may also help scientists to better understand why blood vessels in the choroid become abnormal in eye diseases like age-related macular degeneration.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.32358.001
DOI:
10.7554/eLife.32358.002
DOI:
10.7554/eLife.32358.003
DOI:
10.7554/eLife.32358.005
DOI:
10.7554/eLife.32358.004
DOI:
10.7554/eLife.32358.006
DOI:
10.7554/eLife.32358.007
DOI:
10.7554/eLife.32358.008
DOI:
10.7554/eLife.32358.009
DOI:
10.7554/eLife.32358.010
DOI:
10.7554/eLife.32358.013
DOI:
10.7554/eLife.32358.011
DOI:
10.7554/eLife.32358.012
DOI:
10.7554/eLife.32358.014
DOI:
10.7554/eLife.32358.016
DOI:
10.7554/eLife.32358.015
DOI:
10.7554/eLife.32358.017
DOI:
10.7554/eLife.32358.018
DOI:
10.7554/eLife.32358.020
DOI:
10.7554/eLife.32358.019
DOI:
10.7554/eLife.32358.021
DOI:
10.7554/eLife.32358.022
DOI:
10.7554/eLife.32358.029
DOI:
10.7554/eLife.32358.030
DOI:
10.7554/eLife.32358.024
DOI:
10.7554/eLife.32358.025
DOI:
10.7554/eLife.32358.026
DOI:
10.7554/eLife.32358.027
DOI:
10.7554/eLife.32358.028
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3
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