A variety of gene mutations cause retinitis pigmentosa (RP) – but how do those genes affect the degeneration of rod and cone photoreceptors in the eyes? According to Medical XPress, some researchers wonder if cones are affected due to some issue with sugar metabolism. To develop more targeted therapies which focus on the various mutations and patient needs, researchers evaluated a series of gene therapies in mice models of RP. Ultimately, they determined that Txnip gene therapy is most effective in protecting against vision loss, especially when used in conjunction with other gene therapies. Check out the full study findings published in eLife.

Txnip Gene Therapy

In their research, researchers focused on gene therapies that would impact glucose and sugar metabolism. Altogether, they evaluated 20 potential gene therapies using mice models of RP. Through this, they discovered that:

n adeno-associated virus (AAV) vector expressing Txnip…prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models.

The researchers evaluated the Txnip gene therapy in three separate mice models and found that it was significantly more effective than other options. In particular, C247S, a form of Txnip, helped improve mitochondrial health and allowed cones to use alternate energy sources. As a result, vision was protected.

Next, researchers questioned whether Txnip therapy would be more effective in conjunction with other solutions. To do this, they used specific gene therapies with anti-inflammatory properties that also reduced oxidative stress. Between Txnip and the additional therapies, researchers saw increased cellular protection and better visual acuity.

While these results are promising, additional research is needed to determine if this gene therapy would be similarly effective in human patients with RP.

Retinitis Pigmentosa (RP)

While over 60 gene mutations have been linked to retinitis pigmentosa (RP), a group of genetic diseases, the most common cause are RHO mutations. In fact, up to 30% of RP diagnoses result from these mutations. Depending on the mutation, RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. However, in all cases, RP causes progressive retinal degeneration. Normally, the retina helps convert light into signals. Our brains use this to determine what we’re actually seeing. In patients with RP, as the retina and photoreceptor cells degenerate, so does patients’ vision.

Symptoms vary based on the involvement of rods or cones. For most patients, RP first affects rods at the outer portion of the retina. Thus, initial symptoms include:

• Loss of peripheral vision
• Night vision loss

Once cones become impacted, additional symptoms include:

• Decreased central vision
• Night blindness
• Lowered ability to see colors and details

By age 40, many people with RP are considered to be legally blind.