Molecular markers in Myopia

The following article is presented to you by Barbara Swiatczak
For experts and researchers. The following article may contain statements of complex understanding for the general public.

Myopia occurs when the eye is too long for the focusing power of cornea and lens. This leads to blurred vision in the distance.

What is Myopia?

It can be optically corrected with spectacles but this is no real cure since the eye remains being too long. Eye growth is visually controlled by the retina which analyzes the projected image to guide the eye towards emmetropia. It was shown that for example low temporal and spatial contrast, and low illumination level increase the extent/risk of myopia.

The eye growth and the sign of defocus

The others problems of Myopia

However, the messengers released by retina, retinal pigment epithelium and choroid are largely unknown. Animal models allow us to track changes in molecular pathways during myopia development and facilitate the understanding of this complicated eye growth controlling network. Below you will find three of the most important/best-known signaling molecules involved in eye growth regulation, but there are many more.

Dopamine (DA)

One of the best-known retinal neurotransmitters involved in the control of eye growth by vision. DA is released from dopamine amacrine cells which are positioned within the inner nuclear layer in the retina. DA release displays a diurnal rhythm and is regulated by the retinal illuminance and temporal contrast. Experiments in a number of animal models have shown that a reduced dopamine release is clearly linked to myopia development and that blurred vision leads to a reduction in dopamine content. The level of 3,4-dihydroxyphenylacetic acid (DOPAC) in the vitreous, which is a gel-like substance which fills the space between the lens and retina, is considered a sensitive measure of dopamine release from the retina.

ZENK (also known as Egr-1, Zif268, NGFI-A and Krox-24)

ZENK is a transcription factor (regulating the expression of genetic information) expressed in the retina and the amount of ZENK is controlled by light, especially by transitions between light and darkness. In chicks it was shown that an increase in ZENK expression is detectable already after 15 minutes of wearing negative and positive powered lenses, respectively. Interestingly, the expression of ZENK correlates with the sign of defocus imposed by lenses in a subset of amacrine cells in chicks, specifically the glucagon amacrine cells. Also in mice, the expression of the transcription factor was reduced in form deprived eyes already after 30 minutes. The exact mechanism of these changes are still unknown, but experiments with atropine, which is a drug used to inhibit myopia development, suggest a strongly correlation between suppressed synthesis of ZENK and acceleration of eye growth.

Nitric Oxid  (NO)

It plays an important role as a neuromodulator in eye growth regulation as well as in controlling smooth muscles. It is synthesized by nitric oxide synthase which is expressed widespread in the retina and requires calcium for activation. Experimental delivery of NO sources, like L-Arginine, to the vitreous significantly inhibits the development of form-deprivation myopia. Studies suggest that atropine and dopamine can inhibit eye growth via activating synthesis and release of NO. Nitric oxide itself is not directly inhibiting myopia development but it seems to be an important mediator in the processes controlling eye growth.

Image from a chick retina with choroid and sclera by Barbara Swiatczak

In addition, very recent studies in chicks and mice have shown that the refractive state of the eye and its size depend on the dis-regulation of a range of metabolic and physiologic pathways and not solely on one specific single molecule. These larger transcript networks showed subtle bidirectional expression shifts with hyperopic and myopic defocus. The analysis of differentially expressed genes suggests that extended eye growth is linked to changes in the immune system regulation which can lead to inflammatory responses. Moreover, a dis-regulation in lipid and protein metabolism can influence cell morphology and structure and thereby the development of myopia. Myopia is therefore not “only” an elongation of the eye but involves the disruption of a whole network of biological processes. Still many of these pathways are still unknown. Understanding of the network involved is a huge challenge for the future but more information is necessary to decrease the still rising amount of myopia among the worldwide population

Stay up-to-date, Keep on reading and

Myopia in Science!

  • References.
1. Dopamine signaling and myopia development: What are the key challenges? Xiangtian Zhouab Machelle T. Parduecd P. Michael Iuvoneef Jia Quab
2. An updated view on the role of dopamine in myopia. Marita Feldkaemper, Frank Schaeffel
3. Dopamine and retinal function. Witkovsky P. Doc Ophthalmol. 2004 Jan;108(1):17-40.
4. Retinal dopamine and form-deprivation myopia. R.A. Stone, T. Lin, A.M. Laties, P.M. IuvoneProc. Natl. Acad. Sci. U. S. A., 86 (1989), pp. 704-706
5. Changes in dopamine and ZENK during suppression of myopia in chicks by intense illuminance. W. Lang, Z. Yung, M. Feldkaemper, F. Schaeffel, Exp Eye Res. 2016 Apr;145:118-124.
6. Nitric Oxide (NO) Mediates the Inhibition of Form-Deprivation Myopia by Atropine in Chicks. BJ Carr., WK Stell., Sci Rep. 2016 Dec 5;6(1):9. 
7. Integrated Comparison of GWAS, Transcriptome, and Proteomics Studies Highlights Similarities in the Biological Basis of Animal and Human Myopia. Riddell N., Crewther SG., Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):660-669.
8. Bidirectional Expression of Metabolic, Structural, and Immune Pathways in Early Myopia and Hyperopia. Riddell N., Giummarra L., Hall NE., Crewther SG., Front Neurosci. 2016 Aug 30;10:390.

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