{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:42:18Z","timestamp":1790419338794,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The visual system has served as an expeditious entry point for discerning the mechanism of action of many brain systems, spearheading multiple fields of neuroscience in the process. It has additionally launched the careers of countless scientists, as we have crafted new means to understand neuronal structures and their functions, leading to advances in many areas of the sciences. Indeed, one can readily mark the onset of the scientific examination of the visual system with the 1851 invention of the ophthalmoscope by Hermann von Helmholtz, and the trichromatic theory of color vision in 1802. The Young\u2013Helmholtz understanding the red\u2013green\u2013blue nature of color vision became the foundation to understanding sensory system function that visual artists and also contemporary flat panel displays rely on. It is fascinating to realize that the paintings of Georges Seurat and an iPhone display share a commonality of this application of the trichromatic theory. While it was not until 1956 that the existence of cells responsive to three different ranges of wavelengths was proven with the work of Gunnar Svaetichin, this proof in many ways marked the advancement of tools to visualize at a microscopic level, a full century after the Young\u2013Helmholtz theory was developed. Just a decade later, in 1966, the person widely considered as the founder of modern neuroscience, Stephen Kuffler, founded the Harvard neurobiology department. It was from Kuffler\u2019s work with his post-doctoral students that many new fields of study were created and from whom many of the neuroscience programs across the US were founded. In terms of the visual system, Kuffler and his team were key in detailing areas of retinal neuroanatomy, neurochemistry, neurophysiology, and developmental neurobiology. This paper traces areas in visual system research that provide our understanding of the disparate areas of brain sciences. As such, there are six categories that are evaluated, each of which spawned work in multiple areas that have become mainstays in neuroscience. These range from fields that were dominant a half century ago to ones that have their origins in this decade. The commonality is that all of these owe their origin to Helmholtz and Kuffler, polymaths of the nineteenth and twentieth centuries. We will examine the impact of vision research across the following fields of neuroscience: sensory system function, neuroanatomy, neurochemistry, neurophysiology, developmental neurobiology, and neurological health and disease.<\/jats:p>","DOI":"10.3390\/brainsci15050453","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Window to the Brain\u2014The Enduring Impact of Vision Research"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-8983","authenticated-orcid":false,"given":"George","family":"Ayoub","sequence":"first","affiliation":[{"name":"Psychology Department, University of California, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-vision-091517-034222","article-title":"A Life in Vision","volume":"4","author":"Dowling","year":"2018","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_2","unstructured":"Kolb, H., Fernandez, E., Jones, B., and Nelson, R. (2025, March 14). How the Retina Works (pdf), Webvision: The Organization of the Retina and Visual System, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK610611\/."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tombran-Tink, J., and Barnstable, C.J. (2008). An Organ of Exquisite Perfection. Visual Transduction and Non-Visual Light Perception, Humana Press.","DOI":"10.1007\/978-1-59745-374-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2142\/biophysics.11.61","article-title":"FTIR study of primate color visual pigments","volume":"11","author":"Katayama","year":"2015","journal-title":"Biophysics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/BF01119299","article-title":"The postnatal development of the visual cortex and the influence of environment","volume":"2","author":"Wiesel","year":"1982","journal-title":"Biosci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1113\/jphysiol.1973.sp010381","article-title":"Receptive field organization of bipolar and amacrine cells in the goldfish retina","volume":"235","author":"Kaneko","year":"1973","journal-title":"J. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1113\/jphysiol.1970.sp009084","article-title":"Physiological and morphological identification of horizontal, bipolar and amacrine cells in goldfish retina","volume":"207","author":"Kaneko","year":"1970","journal-title":"J. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1113\/jphysiol.1984.sp015414","article-title":"The release of gamma-aminobutyric acid from horizontal cells of the goldfish (Carassius auratus) retina","volume":"355","author":"Ayoub","year":"1984","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/cne.901820204","article-title":"GABA-ergic pathways in the goldfish retina","volume":"182","author":"Marc","year":"1978","journal-title":"J. Comp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/0921-8696(89)90008-X","article-title":"Release of endogenous glutamate from isolated cone photoreceptors of the lizard","volume":"10","author":"Ayoub","year":"1989","journal-title":"Neurosci. Res. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Boff, J.M., Shrestha, A.P., Madireddy, S., Viswaprakash, N., Della Santina, L., and Vaithianathan, T. (2024). The Interplay between Neurotransmitters and Calcium Dynamics in Retinal Synapses during Development, Health, and Disease. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202401.0998.v1"},{"key":"ref_12","unstructured":"Kolb, H., Fernandez, E., Jones, B., and Nelson, R. (2025, March 14). Neurotransmitters in the Retina by Helga Kolb, Webvision: The Organization of the Retina and Visual System, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK11546\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/293220a0","article-title":"Retinal bipolar cells with double colour-opponent receptive fields","volume":"293","author":"Kaneko","year":"1981","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1017\/S0952523800001954","article-title":"Retinal bipolar cells receive negative feedback input from GABAergic amacrine cells","volume":"1","author":"Tachibana","year":"1988","journal-title":"Vis. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.neuron.2012.10.002","article-title":"The neuronal organization of the retina","volume":"76","author":"Masland","year":"2012","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ichinose, T., and Habib, S. (2022). ON and OFF Signaling Pathways in the Retina and the Visual System. Front. Ophthalmol., 2.","DOI":"10.3389\/fopht.2022.989002"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0006-8993(74)90416-8","article-title":"Autoradiographic demonstration of ocular-dominance columns in the monkey striate cortex by means of transneuronal transport","volume":"79","author":"Wiesel","year":"1974","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Butts, D.A., Kanold, P.O., and Shatz, C.J. (2007). A burst-based \u201cHebbian\u201d learning rule at retinogeniculate synapses links retinal waves to activity-dependent refinement. PLoS Biol., 5.","DOI":"10.1371\/journal.pbio.0050061"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.neuron.2012.06.009","article-title":"Development and plasticity of the primary visual cortex","volume":"75","author":"Espinosa","year":"2012","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wong-Riley, M.T.T. (2021). The critical period: Neurochemical and synaptic mechanisms shared by the visual cortex and the brain stem respiratory system. Proc. Biol. Sci., 288.","DOI":"10.1098\/rspb.2021.1025"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000310398","article-title":"Silent myocardial ischemia in glaucoma patients","volume":"207","author":"Kaiser","year":"1993","journal-title":"Ophthalmologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/eurheartj\/eht023","article-title":"The eye and the heart","volume":"34","author":"Flammer","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1007\/s40123-024-00942-x","article-title":"Oculomics: A Crusade Against the Four Horsemen of Chronic Disease","volume":"13","author":"Patterson","year":"2024","journal-title":"Ophthalmol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100588","DOI":"10.1016\/j.eclinm.2020.100588","article-title":"A machine learning approach for retinal images analysis as an objective screening method for children with autism spectrum disorder","volume":"28","author":"Lai","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Barrett-Young, A., Reuben, A., Caspi, A., Cheyne, K., Ireland, D., Kokaua, J., Ramrakha, S., Tham, Y.-C., Theodore, R., and Wilson, G. (2025). Measures of retinal health successfully capture risk for Alzheimer\u2019s disease and related dementias at midlife. J. Alzheimer\u2019s Dis., 13872877251321114.","DOI":"10.1177\/13872877251321114"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e001594","DOI":"10.1136\/bmjophth-2023-001594","article-title":"Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy","volume":"9","author":"Shi","year":"2024","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s40123-022-00641-5","article-title":"Using Artificial Intelligence to Analyse the Retinal Vascular Network: The Future of Cardiovascular Risk Assessment Based on Oculomics? A Narrative Review","volume":"12","author":"Arnould","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/ICU.0000000000000886","article-title":"Artificial intelligence in retinal imaging for cardiovascular disease prediction: Current trends and future directions","volume":"33","author":"Wong","year":"2022","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ghenciu, L.A., Dima, M., Stoicescu, E.R., Iacob, R., Boru, C., and Ha\u021began, O.A. (2024). Retinal Imaging-Based Oculomics: Artificial Intelligence as a Tool in the Diagnosis of Cardiovascular and Metabolic Diseases. Biomedicines, 12.","DOI":"10.3390\/biomedicines12092150"},{"key":"ref_30","unstructured":"Kolb, H., Fernandez, E., Jones, B., and Nelson, R. (2025, March 19). Cellular Remodeling in Mammalian Retina Induced by Retinal Detachment, Webvision: The Organization of the Retina and Visual System, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK11552\/."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exer.2016.03.027","article-title":"Astrocyte structural reactivity and plasticity in models of retinal detachment","volume":"150","author":"Luna","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"137","DOI":"10.46439\/signaling.2.045","article-title":"Integrating \u201cfast\u201d and \u201cslow\u201d systems therapeutics for physiological renormalization in neurodegenerative disorders","volume":"2","author":"Maguire","year":"2024","journal-title":"Cell Signal"},{"key":"ref_33","first-page":"60","article-title":"Measuring and Treating Retinal Venous Pressure: Efforts and Benefits. Heakthbook TIMES","volume":"3","author":"Flammer","year":"2021","journal-title":"hb TIMES Schw. Aerztej."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.aopr.2025.03.001","article-title":"The Effect of a specific Vitamin Supplement containing L-methylfolate (Ocufolin forte) in Patients with Neovascular Age-Related Macular Degeneration","volume":"5","author":"Josifova","year":"2025","journal-title":"Adv. Ophthalmol. Pract. Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/5\/453\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:22:16Z","timestamp":1760030536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/5\/453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,26]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["brainsci15050453"],"URL":"https:\/\/doi.org\/10.3390\/brainsci15050453","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,26]]}}}