Overview 

The eyes have an incredible range of vision, allowing us to see what we see directly and peripherally. However, in tunnel vision, the eyes lose the ability to see the periphery. They can only see objects close to the visual field’s centre. Tunnel vision arises from conditions that interfere with the rod and cone cells, accountable for peripheral vision. The basis of these conditions can originate from genetic mutations in the eye. In this article, we shall break down the exact role of genetics in various conditions associated with tunnel vision. 

Understanding tunnel vision 

Tunnel vision is where the eyes cannot see an object unless it is near the centre of the visual field.¹ A person with tunnel vision may experience the following symptoms:

• Bumping into objects
• Dizziness 
• Difficulty driving/navigating crowds
• Blurry vision
• Distortion
• Blind spots 
• Flickering spots/ flashes of light
• Trouble seeing at night 

This restricted field of view can be burdensome as it can make day-to-day tasks difficult. To help us make sense of these symptoms, we must understand the conditions associated with tunnel vision.¹

Tunnel vision can be a symptom of: 

• Glaucoma 
• Optic neuritis
• Retinal detachment 
• Retinitis pigmentosa 
• Severe migraines² 

These conditions mainly affect the rod cells in the retina. The retina is the light-sensitive tissue at the back of the eyeball where images are focused on and converted to electrical signals for the brain. Within the retina, the rod and cone cells respond to light. The cone cells are circular and in the centre of the retina. They are responsible for our perception of colour through high light sensitivity. The rod cells work with low light intensities. This helps us see at night and gives us our peripheral vision.³ So, if someone is affected by these conditions, it can inhibit the function of the rod cells. As a result, a person can lose their peripheral vision while the cone cells function normally.¹ 

Role of genetics in tunnel vision-associated conditions 

Genetic basis of retinitis pigmentosa (RP)

RP is what we call a group of diseases that affect the retina. Specifically, the rod cells in the retina slowly break down over time. The impairment of rod cells comes from genetic mutations. This causes a biological dysfunction in the light-receptive cells by triggering injury pathways. These pathways include:

• Apoptosis- programmed cell death
• Light damage - from UV radiation
• Transport dysfunction within the cells
• Endoplasmic reticulum stress - proteins in the cell are not folded correctly

All of these pathways can be responsible for the death of rod cells. Consequently, this limits a person’s low-light visual field and peripheral vision. RP is classified as genetically heterogeneous. This means there are multiple genetic mutations associated with it. The mutations determine the severity of RP experienced by the patient. The most common genes affected are USH2A, RHO and RPGR. Each of these genes can allow us to classify RP even further. We can distinguish between recessive, dominant and X-linked RP cases by identifying which gene was mutated.⁴

Genetics in glaucoma

Glaucoma is an ocular condition which impacts the optic nerve. Damages to the optic nerve prevent the brain from receiving images. Continuous heightened pressure in the eye can irreversibly damage the optic nerve. The pressure comes from a lack of fluid removal in the eye. This damage can progress to complete blindness in one or both eyes. Tunnel vision is a key indicator that glaucoma has reached advanced stages. Glaucoma can develop at any age. Genetic links can help us characterise the type of glaucoma, early onset and adult onset. 

Early onset glaucoma (EOG)

This type of glaucoma has Mendelian inheritance. This means the condition is passed on from parent to offspring in a certain pattern. Some specific genes are accountable for this pattern of inheritance: OPTN, MYOC and CYP1B1. The MYOC gene mutations play a major role in EOG. Missense mutations are most commonly found in this gene. This type of mutation alters the DNA sequence and subsequently the amino acid coded for. Some can result in the most severe form of EOG. Interestingly enough, deleterious mutations are not disease-causing. This indicates that this condition arises from a gain-of-function.⁵

Generally, people who are diagnosed with early-onset glaucoma suffer from the severe form. In the early stages, the patient can be asymptomatic and not experience any symptoms. As a result, we are not able to identify the condition early on, thus making early intervention difficult. This decreases the chances of preventing irreversible damage to the eyes ⁵ 

Adult-onset glaucoma (AOG)

AOG is when glaucoma develops after the age of 40. Genome-wide association studies (GWAS) were carried out. Here, they found a high prevalence of glaucoma in European Caucasian and Asian populations. This identified 16 genes associated with glaucoma. CDKN2BAS, SIX6 and ABCA1 are some genes which were found across the population worldwide. Each gene mutation showed a stronger affinity for specific types of AOG. e.g. CDKN2BAS has a greater link to primary OAG than to normal tension glaucoma.⁵ 

Genetic factors in other neurological conditions 

Tunnel vision can become a secondary symptom in other neurological conditions through a genetic link. 

Migraine

40 genetic loci have been discovered which are associated with migraine. These genetic components can be found through a person’s family history. In severe cases, a person can experience migraine aura. This can come in the form of tunnel vision due to genetic predispositions.⁶ 

Stroke 

After a stroke, some people can experience tunnel vision as a side effect. During a stroke, there can be a loss of vision due to the reduced or excessive blood flow in the brain. This impacts the part of the brain which processes images, the occipital lobe. As a result, the peripheral visual field is lost. This damage to the brain can arise from several genetic risk factors:²

• Cardiovascular issues, such as high blood pressure and high cholesterol, are linked to AGT and ACE genes
• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts ⁷ (CADASIL) was caused by  NOTCH3 mutations
• Sickle cell disease from HBB gene mutations 
• MELAS⁸ syndrome is caused by a mutation in mitochondrial DNA, MT-TL1. This results in stroke-like episodes, which lead to tunnel vision due to damage to visual processing areas

In general, people can have a partial or full visual recovery, depending on the severity of the stroke.  

Diagnostic advances in genetics 

As we have discussed, there are several genetic links to tunnel vision in various conditions. We can use this genetic link to help identify conditions earlier. E.g. running genetic tests allows us to identify pre-symptomatic EOG, and doctors can carry out genetic counselling. Early detection allows for early intervention, which can stunt the advancement of the disease. Targeted genetic therapies can save a person from irreversible blindness.⁵ 

Emerging research and treatment innovations 

For patients with RP, there is no standardised treatment. However, gene therapy has been a promising potential. The eye is an optimal place for targeted gene therapy as it can be easily accessed and isolated. It can be administered with viral vectors, which can then deliver therapeutic genes. Various animal studies demonstrated the possibility of restoring damaged rod cells. In human studies, patients with Leber congenital amaurosis (LCA is an extreme form of RP) were given an injection of AAV. The AAV injection transported the RPE65 gene. This resulted in visual improvements.⁴ 

In addition, stem cell therapies have shown their ability to restore vision in RP patients. In animal studies, the stem cells injected into the eye were integrated into the retina, improving visual function. This is due to the stem cell’s ability to differentiate into the rod cells and replenish the supply. For patients with severe RP, stem cells from the bone marrow can be used to maintain the cone cells in the retina. This works in combination with the Rod precursor cell transplantation. These techniques can be used as an individualised approach.⁴ 

Challenges in genetic research 

While the new upcoming therapies show great potential, there is still a way to go before widespread clinical use. Immune rejection threatens gene therapies. There is also a limit to the amount of cell integration. Furthermore, the genetic mechanisms of these conditions have only recently been explored. As we have learnt, there are several genes associated with specific conditions. Hence, the full range of treatments is yet to be fully realised. Gene-specific and mutation-specific therapies are currently undergoing investigation, which shows great promise for future targeted therapies.⁴

Summary

• Tunnel vision arises from underlying conditions such as RP, glaucoma, strokes or migraines through genetic links
• Research has revealed that specific genetic mutations are the main cause of these conditions
• Early genetic testing for retinal diseases can prevent irreversible damage caused by hereditary conditions
• Personalised therapies can be carried out through specific gene targeting, which can treat tunnel vision 
• Challenges remain due to the complexity of  gene therapy, one gene can impact several other factors in the body
• Stem cells combined with gene editing have been at the forefront of effective treatment and prevention strategies