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Visual Cortex and Molecular Basis of Amblyopia

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Molecular Basis of Amblyopia
Photo: http://biology.usf.edu/

We have promised you the other day that we will explain into further details what pathophysiological mechanisms exactly happen in amblyopia and why this condition arises in the first place. We will discover the human visual cortex, examining it in greater depth, and discuss molecular basis of amblyopia. Lastly, we will briefly cover how it could potentially be treated in the future.

Our Sight is Born Naïve

At birth human brain is rather poorly developed. The visual system, visual brain cortex in particular, is no exception. As intriguing as it is, the exact developmental processes in the brain are hard to study in humans, which is why many useful animal models of vision development were introduced in the last 50 years or so. Human visual cortex is rather complex in its structure, so not just any mammal is appropriate for the study of amblyopia.

Animal Models for Vision Development: Exploring Human Visual Cortex and Amblyopia

Studies have shown though, that the structure of visual cortex in kittens and monkeys share the most similarities to that in humans. Why is that? Well, evolutionary we [humans] are hunters and so are cats. It is of great importance for us as well as cats that we can judge the distance of the objects very accurately, something that binocular vision and the position of our two eyes enable us. Nonetheless, the similarities between us, monkeys and cats end when it comes to absolute developmental time courses of the visual system.

The structure of visual cortex in cats share similarities to that in humans.
The structure of visual cortex in cats share similarities to that in humans.

Much of the research were devoted to address this issue and the verdicts are as following. The development of the visual brain cortex ends at around 8 weeks in kittens, 8 months in monkeys and, most importantly, 8 years in humans.

Critical Period for Vision Development

Those periods are now known as critical periods for vision development. Whereas new studies show, that amblyopia can be improved even beyond the so-called critical period, general recommendations remain that it should be addressed and eliminated within the first 8 years of one’s life.

Another rule also applies for amblyopia – the younger the child that develops it the harder it is to treat and vice versa. That is why amblyopia, which develops due to congenital cataracts is especially hard to treat, if the cataract is not extracted within a few months after birth.

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Unbalanced Eye Inputs in Vision Development: Impact on Synaptic Connections and Binocular Vision

Thus, our sight is very fragile, during the maturation, it is highly influenced by the environment. During the development of vision, billions of new synapses (communications between neurons) are formed.

In healthy individuals, the inputs from the two eyes are rather equal, so the connections formed are very much balanced between the two eyes. In those kids however, in whom the inputs from the two eyes are unequal for whatever reason, the input is highly unbalanced so that the connections from the eye that provides higher quality image prevail over those from the worse eye.

Amblyopia: Brain’s Preference for Better Eye and Lack of Binocular Vision Development

The brain then favours the input from the better eye, which is why vision in the worse eye does not develop as it should. In fact, the inputs from the worse (now amblyopic) eye are slowly but surely being shut down in the brain, for it not to interfere with the best visual acuity one has got.

What is more, due to a monocular instead of binocular viewing, one is also unable to develop binocular vision and hence stereopsis (perception of depth and 3-dimensional image).

Tools to ”Manipulate” Amblyopia

When we treat amblyopia in clinical practice, we try to stimulate the input from the amblyopic eye by forcing the person to use it (patching of the better eye or vision therapy such as AmblyoPlay). Indeed, up to about 8 years of age in humans, this treatment is super effective. The question is then, what happens beyond the so-called critical period for vision development?

Patching of the better eye and doing vision therapy such as AmblyoPlay, we force the worse eye to use it.

Beyond the Critical Period

In the past it was generally accepted, general belief shall we say, that we cannot do much in terms of amblyopia improvement beyond the critical period. Notwithstanding, numerous clinical studies that were publish in the past few decades disprove it.

In fact, with certain interventions improvements are possible not only in adolescence, but even in adulthood. The neurophysiological bases of such improvements, however, remain poorly understood. For that, studying amblyopia recovery in animal models has yielded interesting if not outstanding results.

Following the extensive research of brain plasticity in amblyopia, one of the latest research, that was done in kittens in whom profound amblyopia was induced by suturing one of their eyes in their early lives, shows that there seems to be a way of restoring the suppression of the amblyopic eye.

According to the report, the brain visual cortex in kittens can be reset and hence amblyopia completely eliminated, all of that beyond the critical period for vision development. The secret supposedly lies in the noisy impulses that are coming from the retina of the deprived (amblyopic) eye. Having completely shut down the retinas, the brain would sense that and reboot the whole visual cortex, putting it in a state like that at birth.

Potential Treatment for Amblyopia: Rebooting the Visual Cortex with Tetrodotoxin (TTX)

OK, it all sounds easy on paper, but how on Earth would one be able to completely shut down the retinas without damaging them? The answer lies in the use of a potent neurotoxin, called TTX (tetrodotoxin).

Perhaps some of you has already heard of it. It is a toxin that can be found in certain fish species, most famous being the pufferfish used for the Japanese delicacy – fugu. If not carefully prepared, the eaters can poison themselves or, in the extreme cases, even die.

Food aside, one research group did just that. They injected the TTX into kitten’s eyes and indeed, the brain visual cortex was somehow rebooted, which proves that there are known molecular mechanisms that could lead to a potential pharmacological treatment of (adult) amblyopia in the future.

Conclusion

On that note, which is still more of a science fiction that the reality, I would like to end today’s blog. We hope you have enjoyed. If you have, subscribe to newsletter to stay up-to-date with our blog content and other offers!

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Why Do We Suggest a Minimum Time of 6 Months for Success?

Based on the data from over 15,000 patients using AmblyoPlay, improvements start within 4 months, while optimal results take anywhere between 6-18 months on average. The duration of required training depends on the patient’s age, the severity of the problem, accompanying diseases, and adherence to the training program.