Tomás first noticed something was wrong during an evening walk with friends. They often strolled the country roads outside their small town, their voices carrying in the quiet night. But suddenly, he found it difficult to make out the edges of the road. Shapes blurred at the periphery of his vision. Unbeknownst to him, Tomás was experiencing the early signs of retinitis pigmentosa, a condition characterized by vision loss in low light, often referred to as night blindness.
Retinitis pigmentosa affects approximately one in 4,000 people worldwide, and when combined with other rare genetic vision disorders, the prevalence can rise to as high as one in 2,000 individuals. Understanding how we witness color and light is crucial to understanding this condition, and the impact it has on those affected.
How We See Colors and Lights
The retina, a layer of neural tissue lining the back of the eye, develops as an outgrowth of the central nervous system. It differentiates into distinct, interconnected neuronal layers. Within the retina are specialized light-sensitive cells called photoreceptors – rods and cones – which can be stimulated by even a single photon of light. These cells convert light into chemical and then electrical signals, initiating the process of vision.
The human retina contains around 120 million rods and approximately 7 million cones. Rods are responsible for vision in dim light, activated by low-intensity light photons and a molecule called rhodopsin. They do not perceive color, providing only black and white vision. Cones, respond to high-intensity photons and are responsible for color vision.
An Unequal Distribution
Rods are distributed throughout the retina, whereas cones are concentrated primarily in the macula, the central area of the retina. This high density of cones provides visual acuity, or extreme sensitivity to contrast.
At night, in dim light, only rods can be activated. That’s why we see in black and white when it gets dark and struggle to read, although our peripheral vision remains good. Though, when a flashlight is turned on, or under a streetlamp, the high-intensity photons activate the cones, and we begin to perceive colors and details as we do in daylight.
The Brain Interprets What We See
In retinitis pigmentosa, genetic mutations affecting rod function cause these cells to become altered, stop working, and eventually undergo programmed cell death. This initiates a progressive loss of rods, starting from the periphery and moving inward.
In Tomás’s retina, the disease was progressing unnoticed until the loss of rods affected his visual perception. His night vision was impaired, and he began to experience tunnel vision – difficulty locating surrounding objects, but still being able to read and perceive details because the cones in the macula remained functional.
Over time, the progression of the disease can also affect cones, leading to total blindness.
Symptoms Typically Appear in Late Adolescence
Patients with retinitis pigmentosa usually begin to notice symptoms in late adolescence or adulthood. However, mutations affecting the structural genes of photoreceptors or occurring during development can cause the disease to appear in childhood, as seen in Leber congenital amaurosis. Another congenital condition, achromatopsia, is characterized by the inability to perceive color, with the world appearing in shades of gray.
In other rare retinal pathologies, such as Stargardt disease, mutations affect genes relevant to cones or the macula, leading to their early degeneration. This allows patients to see in low light but impairs their ability to discern fine details, like facial features.
The Search for Treatments
Currently, there are no approved treatments that completely halt the degeneration caused by retinitis pigmentosa.
The design and application of specific advanced therapies requires basic research into the genetic, biochemical, and cellular processes altered by mutations in retinal genes.
This is where biotechnology plays a role, allowing researchers to analyze disease models, either by creating avatar mice (with the condition) or using human retinal organoids – the closest approximation to a human retina in a petri dish.
This research could lead to the development of precision medicine treatments targeting diseases caused by specific genes or mutations – such as Luxturna, for mutations in the RPE65 gene – as well as therapies aimed at photoreceptor survival, without focusing on specific genes or mutations, known as “agnostic” therapies.
These are promising avenues for treating, and potentially even curing, Tomás and other patients with rare inherited retinal diseases.
