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The image above¹ is from Tabulae anatomicae by Bartolomeo Eustachio, a neuroscientist from Italy. The book was not published until 1714 by Pope Clement XI even though the images were made in 1522 by Eustachio.²

Tabulae anatomicae discussed for the first time the correct path of optic nerves and gave diagrams of the optic chiasm.² While the ancient Greeks believed that the optic nerve projected to the lateral ventricles or directly to the brain, Eustachio stated that it projected to the posterior part of thalamus.² This was important as it furthered our understanding of how the information from our eyes made its way to the brain. Future research would need to be done to better understand how the eyes received that information in the first place.

Sources:
(1) https://link.springer.com/article/10.1007/s00381-019-04107-1
(2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644697/

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The image above¹ is from a 1604 book by Johannes Kepler where he reprinted diagrams of the eye made during the 1580s by Felix Platter, a physician from Switzerland.

These diagrams moved the lens towards the pupil and suggested that the retina is the organ of vision. Before Platter, it was thought that the lens was the organ of vision. However, he believe it was the retina due its proximity to the optic nerve.² This was important as the discovery brought us closer to understanding how visual information is processed in the eyes. Platter correctly identified the retina as where the visual information is projected and converted into neural impulses that can be used by the brain which was important for future discoveries about the cells in the area and how this information is captured.

Sources:
(1) http://nivea.psycho.univ-paris5.fr/FeelingSupplements/Glacial_Sphere.htm
(2) https://neuroportraits.eu/portrait/felix-platter.html

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The image above¹ is of Antonie van Leeuwenhoek, a Dutch microbiologist who is most famous for discovering "animalcules" or bacteria. In 1722 he was the first to discover the layer of rods and cones in the eye, further cementing his importance.² Even though he discovered them, he did not understand what they were for. This set the ground work for other scientists, such as Arthur Jacob and Max Schultze, to study these cells further. This was important as knowledge of these cells began with van Leeuwenhoek and was continued in the future by others who looked into them in more depth with more advanced techniques. It would be very important to understand these cells to later understand the role of various photopigments in vision.

Sources:
(1) https://www.britannica.com/biography/Antonie-van-Leeuwenhoek
(2) https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1755-3768.1935.tb04724.x

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The image above¹ is of the Trichromatic Theory.
Thomas Young, a British physicist and physician first proposed that three types of retinal receptors are sufficient for color vision in 1802, laying the basis for this theory.² Based on reason, Young proposed that different wavelengths of visible light activated different photoreceptors.³ He first proposed the colors these receptors were sensitive to were red, yellow, and blue. Later this would be changed to red, green, and violet. Hermann von Helmholtz and others would later expand on this theory to establish Trichromatic Theory as we know it today.³

This was important as it brought us closer to understanding how the photoreceptor cells and pigments in the eye help us process visual information. Young set the foundation for future scientists to look into further and find out more about how exactly the cells worked and what proteins might be involved.

Sources:
(1) https://psychcrumbs.com/the-trichromatic-theory-of-color-vision/
(2) https://neuroportraits.eu/portrait/thomas-young.html
(3) https://www.verywellmind.com/what-is-the-trichromatic-theory-of-color-vision-2795831

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The image above¹ is of German anatomist and physiologist Heinrich Müller who was the first to notice the red color of retinal cells in 1851, a pigment now known as rhodopsin, during experiments looking into the anatomy of the eyes.² However Müller did not understand how rhodopsin functioned, and this was not actively studied until Christian Boll looked into it over 20 years later.³

This discovery was an important first step in determining how the eye converted visual stimuli into electrical signals that could be understood by the brain. Future research into rhodopsin would be necessary to understand its function in vision and connection with disease.

Sources:
(1) https://www.researchgate.net/figure/Heinrich-Mueller-This-image-was-provided-by-his-90-year-old-widow-to-be-published-in_fig5_355799633
(2) https://www.tandfonline.com/doi/full/10.1080/0964704X.2021.1959165
(3) https://neuroportraits.eu/portrait/franz-christian-boll.html

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The image above¹ is of a page from Bartolomeo Panizza's writing. Panizza was an Italian anatomist who showed experimentally that the occipital lobe is essential for vision in 1855. In his book, "Osservazioni sul nervo ottico", or "Observations on the Optic Nerve", Panizza conducted experiments to determine where in the cerebral cortex processed vision.² Panizza would blind animals and trace nerve degeneration. From this he theorized that parts of the thalamus and occipital lobe had functions in vision. Additionally, lesioning parts of the thalamus and occipital lobe resulted in blindness on the contralateral side of the body and confirmed that these areas were essential for vision.²

This was important as it was the first time the occipital lobe was thought to play a role in vision. Panizza's discovery helped further knowledge about how the brain perceived visual stimuli While this discovery even though it was largely ignored by his peers.3 This also brought us closer to understanding visual information captured by the eyes is processed by the brain. However, more work still needed to be done to understand how the eyes processed this information and turns it into signals understandable by the brain.

Sources:
(1) https://www.aspi.unimib.it/collections/object/detail/10739/
(2) https://www.sciencedirect.com/science/article/pii/S0361923002008316
(3) https://pubmed.ncbi.nlm.nih.gov/11074799/

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The image above¹ is of Franz Christian Boll, a German physiologist and histologist who is credited with discovering the function of rhodopsin in 1876.² Boll noticed in frogs the retina is paler after light exposure and would become completely colorless in direct sunlight. However, the color is restored if the animals are kept in the dark after light exposure. Boll concluded that light was responsible for this effect and that these cells were sending information to the brain to visualize light. He then showed these findings to other scientists who presented his results to the Royal Academy of Sciences in Berlin on November 12, 1876.³

This was important as it helped describe the way in which the rods, previously discovered and described by Max Schultze, worked. This finding continued the work of previous researchers and provided a foundation for further research into understanding how the retinal cells collected information from visual stimuli and sent that information to the brain.

Sources:
(1) http://www.museumofoptography.net/People_%28Scientists%29/Entries/2011/8/13_Franz_Christian_Boll.html
(2) https://neuroportraits.eu/portrait/franz-christian-boll.html
(3) https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/bolls

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The image above1 is a modern diagram of rods and cones.
Max Schultze was a German zoologist and cytologist who proposed that rods and cones were the receptors of vision in the retina during 1866. He used histological studies and prior physiology knowledge, by scientists to do this.² Schultze even gave precise dimensions of rods and cones and suggested that they each have different functions in vision.³ He used this information to propose that these cells were important in the sensation of visual stimuli.

This was important as it gave us more information on the anatomy of the eye and how the eye receives sensation from visual stimuli. It also laid the foundation for future discoveries to learn more about how these cells worked and what types of proteins and pigments were required.

Sources:
(1) https://www.researchgate.net/figure/Schematic-diagram-of-vertebrate-rod-and-cone-photoreceptors-The-phototransducing-outer_fig1_216804721
(2) https://nature.berkeley.edu/garbelottoat/wp-content/uploads/hecht-1936.pdf
(3) https://neuroportraits.eu/portrait/max-schultze.html

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The image above¹ is of the chemical structure of vitamin A. Vitamin A was "discovered" through an incremental 130 year process. The most important part of this process for the purposes of George Wald's discovery was when Paul Karrer described the chemical structure of vitamin A in 1932.² Karrer, a Swiss chemist, extracted vitamin A from cod-liver oil and was able to determine its structure, the first time that the chemical structure of a vitamin had been established.³ For this discovery and others, Karrer would share the 1937 Nobel Prize for Chemistry with Sir Norman Haworth.³ The determination of vitamin A's structure came just in time for Wald to determine that the vitamin was present in the retina and was important in vision a year later.

Sources:
(1) https://www.selleckchem.com/datasheet/vitamin-a-S559202-DataSheet.html
(2) https://pubmed.ncbi.nlm.nih.gov/23183288/
(3) https://www.britannica.com/biography/Paul-Karrer

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The image above¹ shows the difference between night blindness and normal vision. In 1925, Louis Sigurd Fridericia, a Danish physician, and Eiler Holm took it upon themselves to determine if vitamin A deficiency was a cause for night blindness.² Previous work had already shown that a deficiency in a factor present in milk and butter was the cause of xerophthalmia and night blindness in humans and that vitamin A deficiency caused xerophthalmia in rats.3

Fridericia and Holm gave one group of rats a diet with butter fat and another group a diet with lard. Both groups were kept in bright light for several days, to bleach their rhodopsin. The rats were then placed in darkness where their eyes were removed sequentially over the course of a few hours and the regeneration of rhodopsin was measured by comparing the reappearance of the purple color of the isolated retinas. The results showed that the lard-fed rats showed a regeneration rate about one third that of those fed butter. This showed that a lack vitamin A in the lard diets was causing the night blindness in the rats.³ This was important as it showed a connection between vitamin A and vision. However, it was still not known what the connection between vitamin A and rhodopsin was. This led multiple researchers, like George Wald, to look more into vitamin A and its connection with vision.

Sources:
(1) https://www.retinasocal.com/nyctalopia-night-blindness-vitreo-retinal-surgeon-torrance-huntington-beach-ca.html
(2) https://pubmed.ncbi.nlm.nih.gov/19892132/
(3) https://academic.oup.com/jn/article/131/6/1647/4686803

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George Wald was born on November 18, 1906 in New York, New York. The son of immigrants, Wald showed an early aptitude and interest in mechanical things and science.¹ After graduating from high school, Wald attended Washington Square College of New York University where he earned a bachelor of science degree in 1927. During his time at NYU, Wald became interested in scientific research which led him to attend Columbia University as a graduate student in zoology where he would study visual acuity in Drosophila.¹

After graduating from Columbia with his PhD in 1932, Wald would be awarded a National Research Council Fellowship in Biology for 1932-1934.¹ Wald begun this fellowship in the laboratories of Otto Warburg and Otto Fritz Meyerhof in Germany where he first identified vitamin A in the retina and showed that it was an important precursor of rhodopsin, thus essential for vision.² For this work, Wald won the 1967 Nobel Prize for Physiology or Medicine alongside two other scientists, Ragnar Arthur Granit and Halden Keffer Hartline, who also researched the mechanisms of vision.³

After his fellowship Wald continued to make contributions to scientific knowledge, especially regarding photopigments in the eye, as well as speaking on multiple social and political issues important to him. Wald died on April 12, 1997 in Cambridge, Massachusetts at age 90 after a very successful and long career.⁴

Sources:
(1) https://www.encyclopedia.com/people/medicine/biochemistry-biographies/george-wald
(2) https://www.britannica.com/biography/George-Wald
(3) https://faculty.washington.edu/chudler/nobel.html
(4) https://www.nobelprize.org/prizes/medicine/1967/wald/biographical/

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The image above¹ shows the inside of the eye of a person diagnosed with night blindness. Night blindness can be caused by multiple different diseases in addition to vitamin A deficiency.1

In 2013, researchers proposed protocols for the treatment and prevention of night blindness based on cases in Sub-Saharan Africa due to high levels of vitamin A deficiency there. For prevention, measures should be taken to increase vitamin A intake though diet. For treatment, high-dose vitamin A supplementation through pills for several weeks. These protocols were found to reduce the prevalence of night blindness and improve eye health.²

Without the discovery of George Wald, we would not understand the link between vitamin A and night blindness which is so useful in modern treatments for the disease. Overall, knowing the link between vitamin A and rhodopsin as well as rhodopsin's importance in the visual system has and continues to improve the lives of numerous individuals worldwide.

Sources
(1) https://bestpractice.bmj.com/topics/en-us/964
(2) https://www.aao.org/education/topic-detail/vitamin-deficiency--subsaharan-africa

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Consultant Ophthalmologist

Sunderland Eye Infirmary

Sunderland

UK

Disclosures

JS has received sponsorship from Novartis, Bayer, and DORC for meeting travel and accommodation. JS was awarded a research grant in 2017 by the British Vitreoretinal Society.

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Can be caused by many disease processes, both inherited and acquired. Differentials that may cause blurred vision made worse by low light levels (e.g., cataracts, myopia, glaucoma) need to be distinguished from true night blindness. Most commonly reported by patients with inherited retinal or cho...