How Blind People Know Day From Night: The Role of Specialized Retina Cells

How can a person who is blind know whether it’s day or night if they can’t detect light? It’s a question that seems simple, yet the answer lies in a fascinating and relatively recently understood part of the eye – specialized neurons called intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells, of which over 25 varieties have been described, according to recent research, allow some individuals to perceive light even without functioning rods and cones.

Simplified drawing of an eye and retinal neurons. Only the cells involved in light reception are drawn: photoreceptors (cones, in red, green and blue, and rods, in gray), a type of neuron that acts as a connection (in pink) between the photoreceptors and the different types of RGCs, marked in different colors. The extensions of these nerve cells, the axons, form the optic nerve. Created by the authors

The key lies in these ipRGCs, which contain a unique pigment called melanopsin. Unlike traditional photoreceptors – the rods and cones responsible for detailed vision and color perception – ipRGCs directly detect light and relay this information to the brain’s suprachiasmatic nucleus, the master circadian pacemaker. This pathway governs our internal biological clock, telling us when it’s day and when it’s night. Recent discoveries published in PLOS One as well suggest ipRGCs play a role in regulating sleep-wake cycles and body temperature.

How ipRGCs Bypass Traditional Vision

What’s remarkable is that this system continues to function even in individuals with certain types of blindness. This is given that ipRGCs can remain intact even when the rods and cones are damaged, as happens in conditions like retinitis pigmentosa. Similarly, they can continue to function even when other retinal ganglion cells are lost due to increased intraocular pressure, as seen in glaucoma, the leading cause of irreversible blindness worldwide.

Neurona melanopsínica teñida con inmunofluorescencia. — Melanopsin neuron stained with immunofluorescence.

This resilience is due to the specialized nature of these neurons. Not all retinal neurons respond to damage in the same way. IpRGCs are among the most resistant in diseases like glaucoma. In glaucoma, retinal ganglion cells die progressively, starting with those in the periphery. This peripheral vision loss often goes unnoticed until it reaches the central region, making glaucoma known as the “silent thief of sight.”

Glaucoma and Peripheral Vision Loss

The insidious nature of glaucoma is compounded by the fact that peripheral vision loss can be difficult to detect in its early stages. Because ipRGCs are more resistant, individuals may maintain some awareness of day and night even as other vision functions decline. However, it’s important to remember that glaucoma is irreversible; damaged neurons cannot regenerate. This underscores the importance of early detection and intervention.

Schematic of the projections of the different neurons of the retina in the brain of a rodent. Some neurons connect with areas that process the visual message and others do so with areas responsible for circadian rhythms, such as the suprachiasmatic nucleus. Created by the authors

Our research group at the University of the Basque Country recently identified that ganglion cells with melanopsin are the most resistant in the early stages of the disease in rats. We know this also happens in human patients, as they are able to tell if it’s day or night despite being blind. Further research is needed to determine which specific retinal ganglion cell subtypes are affected and which are resistant in humans, potentially using advanced imaging techniques like optical coherence tomography (OCT). OCT allows for high-precision visualization of the retinal layers, but currently cannot reliably distinguish between these subtypes.

understanding the vulnerabilities of different neuronal populations could lead to new therapeutic strategies for glaucoma and other conditions that cause blindness. The ongoing work in this field offers hope for preserving vision and improving the quality of life for those affected by these debilitating diseases.