Anatomy and Physiology of Retina and Posterior Segment of the Eye

  • Orhan E. ArslanEmail author


The fact that the retina is readily accessible has a key role in constructing visual images and interacting with the environment and that most of the sensory input is of visual nature affirms the significance of investigative exploration of this part of the visual system. The goal of this work is to recognize the unique cellular characteristics and the neural circuitry of the retina in the posterior segment in primates. To that end an attempt has been made we have attempted to examine the retinal pigment epithelium and its role in the barrier system and the metabolic activity of the retina. We also discussed the characteristics of the photoreceptors and the foveal structure with associated reflexes. The blood flow and associated regulatory mechanisms as well as laminar organization of the optic disc have been explored.


RPE Optic disc Fovea Hyaloid Photopic Scotopic 


  1. 1.
    Sadler TW. Langman’s medical embryology. 11th ed. Baltimore, MD: Wolters Kluwer Health, Lippincott Williams & Wilkins; 2010. p. 335–44.Google Scholar
  2. 2.
    Moore K. Essentials of human embryology. St. Louis, MO: The C.V. Mosby; 1988. p. 170–4.Google Scholar
  3. 3.
    Davis N, Mor E, Ashery-Padan R. Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27. Development. 2011;138(1):127–38.PubMedCrossRefGoogle Scholar
  4. 4.
    Duke-Elder S, Cook C. Normal and abnormal development. Part 1. Embryology. In: Duke-Elder S, editor. System of ophthalmology, vol. 3. London: Henry Kimpton; 1963. p. 190–201.Google Scholar
  5. 5.
    Fieß A, Kölb-Keerl R, Schuster AK, Knuf M, Kirchhof B, Muether PS, Bauer J. Prevalence and associated factors of strabismus in former preterm and full-term infants between 4 and 10 years of age. BMC Ophthalmol. 2017;17(1):228.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Sharma RK, Ehinger BEJ. Development and structure of the retina. In: Kaufman PL, Alm A, editors. Adler’s physiology of the eye. 10th ed. St Louis: Mosby; 2003. p. 319–47.Google Scholar
  7. 7.
    Hartnett M. Pediatric retina. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. p. 710–3.Google Scholar
  8. 8.
    Davis RJ, Alam NM, Zhao C, Müller C, et al. The developmental stage of adult human stem cell-derived retinal pigment epithelium cells influences transplant efficacy for vision rescue. Stem Cell Rep. 2017;9(1):42–9.CrossRefGoogle Scholar
  9. 9.
    Panda-Jonas S, Jonas JB, Jakobczk-Zmija M. Retinal pigment epithelial cell count, distribution and correlations in normal human eyes. Am J Ophthalmol. 1996;121:181–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Boulton M, Dayhaw-Barker P. The role of the retinal epithelium: topographical variation and ageing changes. Eye. 2001;15:384–9.PubMedCrossRefGoogle Scholar
  11. 11.
    La Cour M. The retinal pigment epithelium. In: Kaufman PL, Alm A, editors. Adler’s physiology of the eye. 10th ed. St Louis: Mosby; 2003. p. 348–57.Google Scholar
  12. 12.
    Mander KA, Finnie JW. Loss of Endothelial Barrier Antigen Immunoreactivity in Rat RetinalMicrovessels is Correlated with Clostridium perfringens Type D Epsilon Toxin-induced Damage to the Blood-Retinal Barrier. J Comp Pathol. 2018;158:51.PubMedCrossRefGoogle Scholar
  13. 13.
    Cunha-Vaz JG. The blood-retinal barriers system. Basic concepts and clinical evaluation. Rev Exp Eye Res. 2004;78:715–21.CrossRefGoogle Scholar
  14. 14.
    Davson H. The aqueous humour and the intraocular pressure (chapter 1). In: Davson H, editor. Physiology of the eye. 5th ed. London: Macmillan; 1990. p. 3–95.CrossRefGoogle Scholar
  15. 15.
    Thumann G, Hoffmann S, Hinton DR. Cell biology of the retinal pigment epithelium. In: Ryan SJ, editor. Retina. 4th (ed) ed. St. Louis: Elsevier-Mosby; 2006. p. 137–52.CrossRefGoogle Scholar
  16. 16.
    Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85:845–81.PubMedCrossRefGoogle Scholar
  17. 17.
    Kanski JJ, Milewski SA. Introduction. In: Kanski JJ, Milewski SA, editors. Diseases of the macula. St Louis: Mosby; 2002. p. 1–18.Google Scholar
  18. 18.
    Pleyer U, Pohlmann D. Anatomy and immunology of the eye. Z Rheumatol. 2017;76(8):656–63.PubMedCrossRefGoogle Scholar
  19. 19.
    Moustafa MT, Ramirez C, Schneider K, Atilano SR, Limb GA, Kuppermann BD, Kenney MC. Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Müller Cells. J Ocul Pharmacol Ther. 2017;33(8):610–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Steinberg RH. Interactions between the retinal pigment epithelium and the neural retina. Doc Ophthalmol. 1985;60(4):327–46.PubMedCrossRefGoogle Scholar
  21. 21.
    Congdon NG, Friedman DS, Lietman T. Important causes of visual impairment in the world today. J Am Med Assoc. 2003;290(15):2057–60.CrossRefGoogle Scholar
  22. 22.
    Lightman S, Towler HMA. Diabetic retinopathy. Clin Cornerstone. 2003;5(2):12–21.PubMedCrossRefGoogle Scholar
  23. 23.
    Berlanga-Acosta J, Mendoza-Mari Y, Martínez MD, Valdés-Perez C, Ojalvo AG, Armstrong DG. Expression of cell proliferation cycle negative regulators in fibroblasts of an ischemic diabetic foot ulcer. A clinical case report. Int Wound J. 2013;2:232–6.CrossRefGoogle Scholar
  24. 24.
    Bates NM, Tian J, Smiddy WE, Lee WH, Somfai GM, Feuer WJ, Shiffman JC, Kuriyan AE, Gregori NZ, Kostic M, Pineda S, Cabrera DeBuc D. Relationship between the morphology of the foveal avascular zone, retinal structure, and macular circulation in patients with diabetes mellitus. Sci Rep. 2018;8(1):5355.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Tong L, Vernon SA, Kiel W, Sung V, Orr GM. Association of macular involvement with proliferative retinopathy in type 2 diabetes. Diabet Med. 2001;18(5):388–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Dowling JE. Retinal neurophysiology. In: Albert DA, Jakobiec FA, editors. Principles and practice of ophthalmology. 2nd ed. Philadelphia: Saunders; 2000. p. 1713–29.Google Scholar
  27. 27.
    Lerner AB, Fitzpatrick TB, Calkins E, et al. Mammalian tyrosinase; the relationship of copper to enzymatic activity. J Biol Chem. 1950;187:793–802.PubMedGoogle Scholar
  28. 28.
    Morrison R, Mason K, Frost-Mason S. A cladistic analysis of the evolutionary relationships of the members of the tyrosinase gene family using sequence data. Pigment Cell Res. 1994;7(6):388–93.PubMedCrossRefGoogle Scholar
  29. 29.
    Nusliha A, Dalpatadu U, Amarasinghe B, Chandrasinghe PC, Deen KI. Congenital hypertrophy of retinal pigment epithelium (CHRPE) in patients with familial adenomatous polyposis (FAP); a polyposis registry experience. BMC Res Notes. 2014;7:734.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Georgalas I, Paraskevopoulos T, Symmeonidis C, Petrou P, Koutsandrea C. Peripheral sea-fan retinal neovascularization as a manifestation of chronic rhegmatogenous retinal detachment and surgical management. BMC Ophthalmol. 2014;14:112.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Levin LA. Optic nerve. In: Kaufman PL, Alm A, editors. Adler’s physiology of the eye. 10th ed. St Louis: Mosby; 2003. p. 603–38.Google Scholar
  32. 32.
    Tessier-Lavigne M. Visual processing by the retina. In: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science. 4th ed. New York: McGraw-Hill; 2000. p. 507–22.Google Scholar
  33. 33.
    Gallivan JP, Goodale MA. The dorsal "action" pathway. Handb Clin Neurol. 2018;151:449–66.PubMedCrossRefGoogle Scholar
  34. 34.
    Roof DJ, Makino CL. The structure and function of retinal photoreceptors. In: Albert DA, Jakobiec FA, editors. Principles and practice of ophthalmology. 2nd ed. Philadelphia: Saunders; 2000. p. 1624–73.Google Scholar
  35. 35.
    Larsson J, Harrison C, Jackson J, Oh SM, Zeringyte V. Spatial scale and distribution of neurovascular signals underlying decoding of orientation and eye of origin from fMRI data. J Neurophysiol. 2017;117(2):818–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Williams TD, Wilkinson JM. Position of the fovea centralis with respect to the optic nerve head. Optom Vis Sci. 1992;69:369–77.PubMedCrossRefGoogle Scholar
  37. 37.
    Chapot CA, Euler T, Schubert T. How do horizontal cells 'talk' to cone photoreceptors? Different levels of complexity at the cone-horizontal cell synapse. J Physiol. 2017;595(16):5495–506.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Isenberg SJ. Macular development in the premature infant. Am J Ophthalmol. 1986;101:74–80.PubMedCrossRefGoogle Scholar
  39. 39.
    Sjöstrand J, Rosén R, Nilsson M, Popovic Z. Arrested Foveal development in preterm eyes: thickening of the outer nuclear layer and structural redistribution within the fovea. Invest Ophthalmol Vis Sci. 2017;58(12):4948–58.PubMedCrossRefGoogle Scholar
  40. 40.
    Hendrickson AE. Primate foveal development: a microcosm of current questions in neurobiology. Recent developments. Invest Ophthalmol Vis Sci. 1994;35:3129–33.PubMedGoogle Scholar
  41. 41.
    Hoshino A, Ratnapriya R, Brooks MJ, Chaitankar V, Wilken MS, Zhang C, Starostik MR, Gieser L, La Torre A, Nishio M, Bates O, Walton A, Bermingham-McDonogh O, Glass IA, Wong ROL, Swaroop A, Reh TA. Molecular anatomy of the developing human retina. Dev Cell. 2017;43(6):763–79.PubMedCrossRefGoogle Scholar
  42. 42.
    Callaway EM. Structure and function of parallel pathways in the primate early visual system. J Physiol. 2005;566:13–9.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Sridhar MS. Anatomy of cornea and ocular surface. Indian J Ophthalmol. 2018;66(2):190–4.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Burgi PY, Grzywacz NM. Model for the pharmacological basis of spontaneous synchronous activity in developing retinas. J Neurosci. 1994;14(12):7426–39.PubMedCrossRefGoogle Scholar
  45. 45.
    Wang M, Jin Q, Wang H, Baniasadi N, Elze T. Quantifying positional variation of retinal blood vessels in glaucoma. PLoS One. 2018;13(3):e0193555.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Zhu M, Madigan MC, Van Driel D, Maslim J, Billson F, Provis JM, Penfold PL. The human hyaloid system: cell death and vascular regression. Exp Eye Res. 2000;70:767–76.PubMedCrossRefGoogle Scholar
  47. 47.
    Capelanes NC, Diniz AV, Magalhães ÉP, Marques KO. Comparisons of retinal nerve fiber layer thickness changes after macular hole surgery. Arq Bras Oftalmol. 2018;81(1):37–41.PubMedCrossRefGoogle Scholar
  48. 48.
    Provis JM. Development of the primate retinal vasculature. Prog Ret Eye Res. 2001;20:799–821.CrossRefGoogle Scholar
  49. 49.
    Lee KM, Choung HK, Kim M, Oh S, Kim SH. Positional change of optic nerve head vasculature during axial elongation as evidence of Lamina Cribrosa shifting: Boramae myopia cohort study report 2. Ophthalmology. 2018;pii: S0161–6420(17):32694–5.Google Scholar
  50. 50.
    Horn FK, Mardin CY, Viestenz A, Jünemann AG. Association between localized visual field losses and thickness deviation of the nerve fiber layer in glaucoma. J Glaucoma. 2005;14(6):419–25.PubMedCrossRefGoogle Scholar
  51. 51.
    Hogan MJ, Alvarado JA, Weddell JE. Retina. In: Histology of the human eye. An atlas and textbook, vol. 57. Philadelphia: Saunders; 1971. p. 393–521.Google Scholar
  52. 52.
    Michelessi M, Lucenteforte E, Oddone F, Brazzelli M, Parravano M, Franchi S, Ng SM, Virgili G. Optic nerve head and fibre layer imaging for diagnosing glaucoma. Cochrane Database Syst Rev. 2015;11:CD008803.PubMedCentralGoogle Scholar
  53. 53.
    Erwin E, Baker FH, Busen WF, Malpeli JG. Relationship between laminar topology and retinotopy in the rhesus lateral geniculate nucleus: results from a functional atlas. J Comp Neurol. 1999;407(1):92–102.PubMedCrossRefGoogle Scholar
  54. 54.
    Fitzgibbon T. The human fetal retinal nerve fiber layer and optic nerve head: a DiI and DiA tracing study. Vis Neurosci. 1997;14:433–47.PubMedCrossRefGoogle Scholar
  55. 55.
    Akahori T, Iwase T, Yamamoto K, Ra E, Terasaki H. Changes in choroidal blood flow and morphology in response to increase in intraocular pressure. Invest Ophthalmol Vis Sci. 2017;58(12):5076–85.PubMedCrossRefGoogle Scholar
  56. 56.
    Ranjan R, Manayath GJ, Avadhani U, Narendran V. Rapid macular hole formation and closure in a vitrectomized eye following rhegmatogenous retinal detachment repair. Oman J Ophthalmol. 2018;11(1):71–4.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Newell F. Anatomy and embryology. In: Newell F, editor. Ophthalmology. Principles and concepts. 8th ed. St. Louis: Mosby; 1996. p. 3–73.Google Scholar
  58. 58.
    Fouquet S, Vacca O, Sennlaub F, Paques M. The 3D retinal capillary circulation in pigs reveals a predominant serial organization. Invest Ophthalmol Vis Sci. 2017;58(13):5754–63.PubMedCrossRefGoogle Scholar
  59. 59.
    Vicol AD, Bogdănici T, Bogdănici C. Retinal vascular changes--predictive and prognostic factor in systemic disease. Oftalmologia. 2014;58(1):18–26.PubMedGoogle Scholar
  60. 60.
    Chen TL, Yarng SS. Vitreous hemorrhage from a persistent hyaloid artery. Vitreous hemorrhage from a persistent hyaloid artery. Retina. 1993;13(2):148–51.PubMedCrossRefGoogle Scholar
  61. 61.
    Struijker-Boudier HAJ. Retinal microcirculation and early mechanisms of hypertension. Hypertension. 2008;51:821–2.PubMedCrossRefGoogle Scholar
  62. 62.
    Olver JM, McCartney ACE. Orbital and ocular microvascular corrosion casting in man. Eye. 1989;3:588–96.PubMedCrossRefGoogle Scholar
  63. 63.
    Olver JM, Spalton DJ, McCartney ACE. Microvascular study of the retrolaminar optic nerve in man: the possible significance on anterior ischaemic optic neuropathy. Eye. 1990;4:7–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Takkar B, Azad S, Shakrawal J, Gaur N, Venkatesh P. Blood flow pattern in a choroidal hemangioma imaged on swept-source-optical coherence tomography angiography. Indian J Ophthalmol. 2017;65(11):1240–2.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Leung H, Wang JJ, Rochtchina E, Wong TY, Klein R, Mitchell P. Impact of current and past blood pressure on retinal arteriolar diameter in an older population. J Hypertens. 2004;22:1543–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Paques M, Tadayoni R, Sercombe R, Laurent P, Genevois O, Gaudric A, Vicaut E. Structural and hemodynamic analysis of the mouse retinal microcirculation. Invest Ophthalmol Vis Sci. 2003;44(11):4960–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Conway MD, Stern E, Enfield DB, Peyman GA. Management of cataract in uveitis patients. Curr Opin Ophthalmol. 2018;29(1):69–74.PubMedCrossRefGoogle Scholar
  68. 68.
    Brennan N, Petrou P, Reekie I, Pasu S, Kinsella M, Da Cruz L. Vitrectomy in phacoanaphylactic glaucoma secondary to posterior capsular rupture in an adult with persistent hyperplastic primary vitreous. Retin Cases Brief Rep. 2018;12(2):103–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Moore AT, Michaelides M. Vitreous (chapter 49). In: Taylor D, Hoyt CS, editors. Pediatric ophthalmology and strabismus. 3rd ed. Edinburgh: Elsevier Saunders; 2005. p. 472–85.Google Scholar
  70. 70.
    Fielder AR, Quinn GE. Retinopathy of prematurity (chapter 51). In: Taylor D, Hoyt CS, editors. Pediatric ophthalmology and strabismus. 3rd ed. Edinburgh: Elsevier Saunders; 2005. p. 506–30.Google Scholar
  71. 71.
    Nicholson L, Vazquez-Alfageme C, Patrao NV, Triantafyllopolou I, Bainbridge JW, Hykin PG, Sivaprasad S. Retinal nonperfusion in the posterior pole is associated with increased risk of neovascularization in central retinal vein occlusion. Am J Ophthalmol. 2017;182:118–25.PubMedCrossRefGoogle Scholar
  72. 72.
    Lutty GA, McLeod DS. Retinal vascular development and oxygen-induced retinopathy: a role for adenosine. Prog Ret Eye Res. 2003;22:95–111.CrossRefGoogle Scholar
  73. 73.
    McLeod DS, Baba T, Bhutto IA, Lutty GA. Co-expression of endothelial and neuronal nitric oxide synthases in the developing vasculatures of the human fetal eye. Graefes Arch Clin Exp Ophthalmol. 2012;250(6):839–48.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Strittmatter K, Pomeroy H, Marneros AG. Targeting platelet-derived growth factor receptor β(+) scaffold formation inhibits choroidal neovascularization. Am J Pathol. 2016;186(7):1890–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Kim SJ, Campbell JP, Ostmo S, Jonas KE, Chan RVP, Chiang MF. Imaging and informatics in retinopathy of prematurity (i-ROP) research consortium. Changes in relative position of choroidal versus retinal vessels in preterm infants. Invest Ophthalmol Vis Sci. 2017;58(14):6334–41.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Selvam S, Kumar T, Fruttiger M. Retinal vasculature development in health and disease. Prog Retin Eye Res. 2018;63:1–19.PubMedCrossRefGoogle Scholar
  77. 77.
    Öner A. Recent advancements in gene therapy for hereditary retinal dystrophies. Turk J Ophthalmol. 2017;47(6):338–43.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Chow LC, Wright KW, Sola A. The CSMC oxygen administration study group: can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants? Pediatrics. 2003;111:339–45.PubMedCrossRefGoogle Scholar
  79. 79.
    Kalaie S, Gooya A. Vascular tree tracking and bifurcation points detection in retinal images using a hierarchical probabilistic model. Comput Methods Prog Biomed. 2017;151:139–49.CrossRefGoogle Scholar
  80. 80.
    Oyster C. The retina in vivo and the optic nerve (chapter 16). In: Oyster C, editor. The human eye – structure and function. Sunderland, MA: Sinauer Associates; 1999. p. 701–51.Google Scholar
  81. 81.
    Spaide RF. Choriocapillaris flow features follow a power law distribution: implications for characterization and mechanisms of disease progression. Am J Ophthalmol. 2016;170:58–67.PubMedCrossRefGoogle Scholar
  82. 82.
    Murphy L, Carroll G. Acute bilateral retinal artery occlusion causing sudden blindness in 25-year-old patient. Am J Emerg Med. 2018;pii: S0735–6757(18):30204–3.Google Scholar
  83. 83.
    Chen X, Rahimy E, Sergott RC, Nunes RP, Souza EC, Choudhry N, Cutler NE, Houston SK, Munk MR, Fawzi AA, Mehta S, Hubschman JP, Ho AC, Sarraf D. Spectrum of retinal vascular diseases associated with paracentral acute middle maculopathy. Am J Ophthalmol. 2015;160(1):26–34.e1.PubMedCrossRefGoogle Scholar
  84. 84.
    Bagheri N, Mehta S. Acute vision loss. Prim Care. 2015;42(3):347–61.PubMedCrossRefGoogle Scholar
  85. 85.
    Kita Y, Inoue M, Kita R, Sano M, Orihara T, Itoh Y, Hirota K, Koto T, Hirakata A. Changes in the size of the foveal avascular zone after vitrectomy with internal limiting membrane peeling for a macular hole. Jpn J Ophthalmol. 2017;61(6):465–71.PubMedCrossRefGoogle Scholar
  86. 86.
    Goldmann EE. Vitalfärbung am Zentralnervensystem. Abhandl Königl Preuss Akad Wiss. 1913;1:1–60.Google Scholar
  87. 87.
    Harris A, Ciulla TA, Chung HS, Martin B. Regulation of retinal and optic nerve blood flow. Arch Ophthalmol. 1998;116:1491–5.PubMedCrossRefGoogle Scholar
  88. 88.
    Funk RHW. Blood supply of the retina. Ophthalmic Res. 1997;29:320–5.PubMedCrossRefGoogle Scholar
  89. 89.
    Delaey C, Van de Voorde J. Regulatory mechanisms in the retinal and choroidal circulation. Rev Ophthalmic Res. 2000;32:249–56.CrossRefGoogle Scholar
  90. 90.
    Hao H, Sasongko MB, Wong TY, Che Azemin MZ, Aliahmad B, Hodgson L, Kawasaki R, Cheung CY, Wang JJ, Kumar DK. Does retinal vascular geometry vary with cardiac cycle? Invest Ophthalmol Vis Sci. 2012;53(9):5799–805.PubMedCrossRefGoogle Scholar
  91. 91.
    Hossler FE, Olson KR. Microvasculature of the avian eye: studies on the eye of the duckling with microcorrosion casting, scanning electron microscopy, and stereology. Am J Anat. 1984;170(2):205–21.PubMedCrossRefGoogle Scholar
  92. 92.
    Daxer A. The fractal geometry of proliferative diabetic retinopathy: implications for the diagnosis and the process of retinal vasculogenesis. Curr Eye Res. 1993;12:1103–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Wilson C, Theodorou M, Cocker KD, Fielder A. The temporal retinal blood vessels and preterm birth. Br J Ophthalmol. 2006;90(6):702–4.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Girkin CA, Fazio MA, Yang H, Reynaud J, Burgoyne CF, Smith B, Wang L, Downs JC. Variation in the three-dimensional Histomorphometry of the normal human optic nerve head with age and race: Lamina Cribrosa and Peripapillary scleral thickness and position. Invest Ophthalmol Vis Sci. 2017;58(9):3759–69.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Kanski JJ, Nischal KK. The optic disc. In: Ophthalmology. Clinical signs and differential diagnosis. St Louis: Mosby; 1999. p. 247–85.Google Scholar
  96. 96.
    Varma R, Douglas GR, Steinmann WC, Wijsman K, Mawson D, Spaeth GL. A comparative evaluation of three methods of analyzing optic disc topography. Ophthalmic Surg. 1989;20(11):813–9.PubMedGoogle Scholar
  97. 97.
    Abalo-Lojo JM, Treus A, Arias M, Gómez-Ulla F, Gonzalez F. Longitudinal study of retinal nerve fiber layer thickness changes in a multiple sclerosis patients cohort: a long term 5 year follow-up. Mult Scler Relat Disord. 2018;19:124–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Mataki N, Tomidokoro A, Araie M, Iwase A. Morphology of the optic disc in the Tajimi study population. Jpn J Ophthalmol. 2017;61(6):441–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Jurišić D, Novak Lauš K, Sesar I, Kuzman T. Comparison of optic nerve head morphology in patients with primary open angle glaucoma and non-arteritic anterior ischemic optic neuropathy. Acta Clin Croat. 2017;56(2):227–35.PubMedCrossRefGoogle Scholar
  100. 100.
    Ballae Ganeshrao S, Turpin A, McKendrick AM. Sampling the visual field based on individual retinal nerve fiber layer thickness profile. Invest Ophthalmol Vis Sci. 2018;59(2):1066–74.PubMedCrossRefGoogle Scholar
  101. 101.
    Roth G, Grunwald W, Dicke U. Morphology, axonal projection pattern, and responses to optic nerve stimulation of thalamic neurons in the fire-bellied toad Bombina orientalis. J Comp Neurol. 2003;461(1):91–110.PubMedCrossRefGoogle Scholar
  102. 102.
    Jonas J, Garway-Heath T. Primary glaucomas: optic disc features. In: Hitchings RA, editor. Glaucoma. London: BMJ books; 2000. p. 29–38.Google Scholar
  103. 103.
    Yu PK, Balaratnasingam C, Morgan WH, Cringle SJ, McAllister IL, Yu DY. The structural relationship between the microvasculature, neurons, and glia in the human retina. Invest Ophthalmol Vis Sci. 2010;51(1):447–58.PubMedCrossRefGoogle Scholar
  104. 104.
    Anderson DR. Ultrastructure of the optic nerve head. Arch Ophthalmol. 1970;83(1):63–73.PubMedCrossRefGoogle Scholar
  105. 105.
    Cohen AI. New evidence supporting the linkage to extracellular space of outer segment saccules of frog cones but not rods. J Cell Biol. 1968;37(2):424–44.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Anderson DR. Ultrastructure of human a, d monkey lamina cribrosa and optic nerve head. Arch Ophthalmol. 1969;82(6):800–14.PubMedCrossRefGoogle Scholar
  107. 107.
    Mokhtari M, Rabbani H, Mehri-Dehnavi A, Kafieh R. Exact localization of breakpoints of retinal pigment epithelium in optical coherence tomography of optic nerve head. Conf Proc IEEE Eng Med Biol Soc. 2017;2017:1505–8.PubMedGoogle Scholar
  108. 108.
    Li D, Li T, Paschalis EI, Wang H, Taniguchi EV, Choo ZN, Shoji MK, Greenstein SH, Brauner SC, Turalba AV, Pasquale LR, Shen LQ. Optic nerve head characteristics in chronic angle closure glaucoma detected by swept-source OCT. Curr Eye Res. 2017;42(11):1450–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Duke-Elder S, Wybar KC. System of ophthalmology, the anatomy of the visual system, vol. 2. London: Kimpton; 1961. p. 286–93.Google Scholar
  110. 110.
    Na KI, Lee WJ, Kim YK, Park KH, Jeoung JW. Evaluation of retinal nerve Fiber layer thinning in myopic glaucoma: impact of optic disc morphology. Invest Ophthalmol Vis Sci. 2017;58(14):6265–72.PubMedCrossRefGoogle Scholar
  111. 111.
    Levitzky M, Henkind P. Angioarchitecture of the optic nerve. II Lamina cribrosa. Am J Ophthalmol. 1969;68(6):986–96.PubMedCrossRefGoogle Scholar
  112. 112.
    Bron AJ, Tripathi RC, Tripathy BJ. Optic nerve, section 15.1. Wolff’s anatomy of the eye and orbit. 8th ed. London: Chapman & Hall; 1997. p. 489–535.Google Scholar
  113. 113.
    Büssow H. The astrocytes in the retina and optic nerve head of mammals: a special glia for the ganglion cell axons. Cell Tissue Res. 1980;206(3):367–78.PubMedCrossRefGoogle Scholar
  114. 114.
    Cohen AI. Ultrastructural aspects of the human optic nerve. Investig Ophthalmol. 1967;6(3):294–308.Google Scholar
  115. 115.
    Hondur G, Göktaş E, Al-Aswad L, Tezel G. Age-related changes in the peripheral retinal nerve fiber layer thickness. Clin Ophthalmol. 2018;12:401–9.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Danias J, Shen F, Goldblum D, Chen B, Ramos-Esteban J, Podos SM, Mittag T. Cytoarchitecture of the retinal ganglion cells in the rat. Invest Ophthalmol Vis Sci. 2002;43(3):587–94.PubMedGoogle Scholar
  117. 117.
    Krzyżanowska-Berkowska P, Melińska A, Helemejko I, Robert Iskander D. Evaluating displacement of lamina cribrosa following glaucoma surgery. Graefes Arch Clin Exp Ophthalmol. 2018;256(4):791–800.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Radius RL, Gonzales M. Anatomy of the lamina cribrosa in human eyes. Arch Ophthalmol. 1981;99(12):2159–62.PubMedCrossRefGoogle Scholar
  119. 119.
    Liu B, Kilpatrick JI, Lukasz B, Jarvis SP, McDonnell F, Wallace DM, Clark AF, O'Brien CJ. Increased substrate stiffness elicits a Myofibroblastic phenotype in human Lamina CribrosaCells. Invest Ophthalmol Vis Sci. 2018;59(2):803–14.PubMedCrossRefGoogle Scholar
  120. 120.
    Bernstein SL, Meister M, Zhuo J, Gullapalli RP. Postnatal growth of the human optic nerve. Eye (Lond). 2016;30(10):1378–80.CrossRefGoogle Scholar
  121. 121.
    Wong VK. Retinal venous occlusive disease. Hawaii Med J. 1997;56(10):289–91.PubMedGoogle Scholar
  122. 122.
    Wu Z, Medeiros FA. Recent developments in visual field testing for glaucoma. Curr Opin Ophthalmol. 2018;29(2):141–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Kline LB, Bajandas FJ. Visual fields. In: Kline LB, Bajandas FJ, editors. Neuro ophthalmology. Review manual. 5th ed. Thorofare: Slack; 2004. p. 1–45.Google Scholar
  124. 124.
    Masuda H, Mori M, Uzawa A, Muto M, Uchida T, Ohtani R, Akiba R, Yokouchi H, Yamamoto S, Kuwabara S. Recovery from optic neuritis attack in neuromyelitis optica spectrum disorder and multiple sclerosis. J Neurol Sci. 2016;367:375–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Backner Y, Kuchling J, Massarwa S, et al. Anatomical wiring and functional networking changes in the visual system following optic neuritis. JAMA Neurol. 2018;75(3):287–95.PubMedCrossRefGoogle Scholar
  126. 126.
    Liu GT, Volpe NJ, Galetta SL. Vision loss: retinal disorders of neuro-ophthalmic interest. In: Liu GT, Volpe NJ, Galetta SL, editors. Neuro-ophthalmology. Diagnosis and management. Philadelphia: Saunders; 2001. p. 58–102.Google Scholar
  127. 127.
    Glisson CC. Visual loss due to optic chiasm and retrochiasmal visual pathway lesions. Continuum (Minneap Minn). 2014;20(4 Neuro-ophthalmology):907–21.Google Scholar
  128. 128.
    Zhao Y, Tan S, Chan TCY, Xu Q, Zhao J, Teng D, Fu H, Wei S. Clinical features of demyelinating optic neuritis with seropositive myelinoligodendrocyte glycoprotein antibody in Chinese patients. Br J Ophthalmol. 2018.; pii: bjophthalmol-2017-311177Google Scholar
  129. 129.
    Simpson HD, Kita EM, Scott EK. Goodhill GJ. A quantitative analysis of branching, growth cone turning, and directed growth in zebrafish retinotectal axon guidance. J Comp Neurol. 2013;521(6):1409–29.PubMedCrossRefGoogle Scholar
  130. 130.
    Guillery RW. Developmental neurobiology: preventing midline crossings. Curr Biol. 2003;13:R871–2.PubMedCrossRefGoogle Scholar
  131. 131.
    Van Horck FPG, Weinl C, Holt CE. Retinal axon guidance: novel mechanisms for steering. Curr Opin Neurobiol. 2004;14:61–6.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Giacci MK, Bartlett CA, Huynh M, Kilburn MR, Dunlop SA, Fitzgerald M. Three dimensional electron microscopy reveals changing axonal and myelin morphology along normal and partially injured optic nerves. Sci Rep. 2018 Mar 5;8(1):3979.
  133. 133.
    Rancic A, Filipovic N, Marin Lovric J, Mardesic S, Saraga-Babic M, Vukojevic K. Neuronal differentiation in the early human retinogenesis. Acta Histochem. 2017;119(3):264–72.PubMedCrossRefGoogle Scholar
  134. 134.
    Gonzalez-Fernandez F. Evolution of the visual cycle: the role of retinoid-binding proteins. J Endocrinol. 2002;175:75–88.PubMedCrossRefGoogle Scholar
  135. 135.
    Bock AS, Binda P, Benson NC, Bridge H, Watkins KE, Fine I. Resting-state retinotopic organization in the absence of retinal input and visual experience. J Neurosci. 2015;35(36):12366–82.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    He S, Dong W, Deng Q, Weng S, Sun W. Seeing more clearly: recent advances in understanding retinal circuitry. Science. 2003;302:408–11.PubMedCrossRefGoogle Scholar
  137. 137.
    Rasmussen RS, Schaarup AMH, Overgaard K. Therapist-assisted rehabilitation of visual function and hemianopia after brain injury: intervention study on the effect of the neuro vision technology rehabilitation program. JMIR Res Protoc. 2018;7(2):e65.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    van Wermeskerken M, van der Kamp J, Hoozemans MJ, Savelsbergh GJ. Catching moving objects: differential effects of background motion on action mode selection and movement control in 6- to 10-month-old infants. Dev Psychobiol. 2015;57(8):921–34.PubMedCrossRefGoogle Scholar
  139. 139.
    Yang J, Watanabe J, Kanazawa S, Nishida S, Yamaguchi MK. Infants' visual system nonretinotopically integrates color signals along a motion trajectory. J Vis. 2015;15(1):25.PubMedCrossRefGoogle Scholar
  140. 140.
    Birch EE. Stereopsis in infants and its developmental relation to visual acuity. In: Simons K, editor. Early visual development, normal and abnormal. New York/Oxford: Oxford University; 1993. p. 224–36.Google Scholar
  141. 141.
    Tu JH, Foote KG, Lujan BJ, Ratnam K, Qin J, Gorin MB, Cunningham ET Jr, Tuten WS, Duncan JL, Roorda A. Dysflective cones: visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis. Am J Ophthalmol Case Rep. 2017;7:14–9.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Akbas E, Eckstein MP. Object detection through search with a foveated visual system. PLoS Comput Biol. 2017;13(10):e1005743.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Kompaniez-Dunigan E, Abbey CK, Boone JM, Webster MA. Visual adaptation and the amplitude spectra of radiological images. Cogn Res Princ Implic. 2018;3(1):3.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Norcia AM, Manny RE. Development of vision in infancy (chapter 21). In: Kaufman PL, Alm A, editors. Adler’s physiology of the eye. 10th ed. St Louis: Mosby; 2003. p. 531–51.Google Scholar
  145. 145.
    Sakmar TP. Color vision (chapter 23). In: Kaufman PL, Alm A, editors. Adler’s physiology of the eye. 10th ed. St Louis: Mosby; 2003. p. 578–85.Google Scholar
  146. 146.
    Hughes S, Jagannath A, Rodgers J, Hankins MW, Peirson SN, Foster RG. Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells. Eye (Lond). 2016;30(2):247–54.CrossRefGoogle Scholar
  147. 147.
    Oide M, Okajima K, Nakagami H, Kato T, Sekiguchi Y, Oroguchi T, Hikima T, Yamamoto M, Nakasako M. Blue light-excited LOV1 and LOV2 domains cooperatively regulate the kinase activity of full-length phototropin2 from Arabidopsis. J Biol Chem. 2018;293(3):963–72.PubMedCrossRefGoogle Scholar
  148. 148.
    Foster RG, Wulff K. The rhythm of rest and excess. Nat Rev Neurosci. 2005;6:407–14.PubMedCrossRefGoogle Scholar
  149. 149.
    Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci. 2003;26:314–20.PubMedCrossRefGoogle Scholar
  150. 150.
    Vartanian GV, Zhao X, Wong KY. Using flickering light to enhance nonimage-forming visual stimulation in humans. Invest Ophthalmol Vis Sci. 2015;56(8):4680–8.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Foster RG. Keeping an eye on the time. The Cogan lecture. Invest Ophthalmol Vis Sci. 2002;43:1286–98.PubMedGoogle Scholar
  152. 152.
    Detwiler PB. Phototransduction in retinal ganglion cells. Yale J Biol Med. 2018;91(1):49–52.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Hannibal J, Fahrenkrug J. Melanopsin: a novel photopigment involved in the photoentrainment of the brain’s biological clock? Ann Med. 2002;34:401–7.PubMedCrossRefGoogle Scholar
  154. 154.
    Lucas RJ, Hattar S, Takao M, Berson DM, Foster RG, Yau KW. Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science. 2003;299:245–7.PubMedCrossRefGoogle Scholar
  155. 155.
    Qiu X, Kumbalsiri T, Carlson SM, Wong KY, Krishna V, Provencio I, Berson DM. Induction of photosensitivity by heterologous expression of melanopsin. Nature. 2005;433:745–9.PubMedCrossRefGoogle Scholar
  156. 156.
    García-Ayuso D, Galindo-Romero C, Di Pierdomenico J, Vidal-Sanz M, Agudo-Barriuso M, Villegas Pérez MP. Light-induced retinal degeneration causes a transient downregulation of melanopsin in the rat retina. Exp Eye Res. 2017;161:10–6.PubMedCrossRefGoogle Scholar
  157. 157.
    Pepe IM. Recent advances in our understanding of rhodopsin and phototransduction. Prog Ret Eye Res. 2001;20:733–59.CrossRefGoogle Scholar
  158. 158.
    Morshedian A, Fain GL. Light adaptation and the evolution of vertebrate photoreceptors. J Physiol. 2017;595(14):4947–60.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Arshavsky VY, Lamb TD, Pugh EN Jr. G proteins and phototransduction. Annu Rev Physiol. 2002;64:153–87.PubMedCrossRefGoogle Scholar
  160. 160.
    Shimmura T, Nakayama T, Shinomiya A, Fukamachi S, Yasugi M, Watanabe E, Shimo T, Senga T, Nishimura T, Tanaka M, Kamei Y, Naruse K, Yoshimura T. Dynamic plasticity in phototransduction regulates seasonal changes in color perception. Nat Commun. 2017;8(1):412.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Jerath R, Cearley SM, Barnes VA, Nixon-Shapiro E. How lateral inhibition and fast retinogeniculo-cortical oscillations create vision: a new hypothesis. Med Hypotheses. 2016;96:20–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Xiao M, Hendrickson A. Spatial and temporal expression of short, long/medium, or both opsins in human fetal cones. J Comp Neurol. 2000;425:545–59.PubMedCrossRefGoogle Scholar
  163. 163.
    O’Brien KMB, Schulte D, Hendrickson AE. Expression of photoreceptor-associated molecules during human fetal eye development. Mol Vis. 2003;9:401–9.PubMedGoogle Scholar
  164. 164.
    Glushakova LG, Timmers AM, Pang J, Teusner JT, William W. Hauswirth human blue-opsin promoter preferentially targets reporter gene expression to rat s-cone photoreceptors. Invest Ophthalmol Vis Sci. 2006;47:3505–13.PubMedCrossRefGoogle Scholar
  165. 165.
    Kohl S, Biskup S. Genetic diagnostic testing in inherited retinal dystrophies. Klin Monatsbl Augenheilkd. 2013;230(3):243–6.PubMedGoogle Scholar
  166. 166.
    Campa C, Gallenga CE, Bolletta E, Perri P. The role of gene therapy in the treatment of retinal diseases: a review. Curr Gene Ther. 2017;17(3):194–213.PubMedCrossRefGoogle Scholar
  167. 167.
    Weleber RG, Gregory-Evans K. Retinitis pigmentosa and allied disorders. In: Ryan SJ, editor. Retina. 4th ed. St. Louis: Elsevier-Mosby; 2006. p. 395–498.CrossRefGoogle Scholar
  168. 168.
    Hargrave PA. Rhodopsin structure, function, and topography. The Friedenwald lecture. IOVS. 2001;42:3–9.Google Scholar
  169. 169.
    Omodaka K, An G, Tsuda S, Shiga Y, Takada N, Kikawa T, Takahashi H, Yokota H, Akiba M, Nakazawa T. Classification of optic disc shape in glaucoma using machine learning based on quantified ocular parameters. PLoS One. 2017;12(12):e0190012.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Chalupa LM, Günhan E. Development of On and Off retinal pathways and retinogeniculate projections. Prog Ret Eye Res. 2004;23:31–51.CrossRefGoogle Scholar
  171. 171.
    Valdez DJ, Nieto PS, Díaz NM, Garbarino-Pico E, Guido ME. Differential regulation of feeding rhythms through a multiple-photoreceptor system in an avian model of blindness. FASEB J. 2013;27(7):2702–12.PubMedCrossRefGoogle Scholar
  172. 172.
    Freedman MS, Lucas RJ, Soni B, et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science. 1999;284:502–4.PubMedCrossRefGoogle Scholar
  173. 173.
    Van Gelder RN, Buhr ED. Ocular photoreception for circadian rhythm entrainment in mammals. Ann Rev Vis Sci. 2016;2:153–69.CrossRefGoogle Scholar
  174. 174.
    Lucas RJ, Freedman MS, Munoz M, Garcia-Fernandez JM, Foster RG. Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science. 1999;284:505–7.PubMedCrossRefGoogle Scholar
  175. 175.
    Foster RG, Hankins MW. Non-rod, non-cone photoreception in the vertebrates. Prog Ret Eye Res. 2002;21:507–27.CrossRefGoogle Scholar
  176. 176.
    Gamlin PDR, McDougal DH, Pokorny J, Smith VC, Yau K-W, Dacey DM. Human and macaque pupil responses driven by melanopsin-containing retinal ganglion cells. Vis Res. 2007;47:946–54.PubMedCrossRefGoogle Scholar
  177. 177.
    Hang CY, Kitahashi T, Parhar IS. Neuronal organization of deep brain opsin photoreceptors in adult teleosts. Front Neuroanat. 2016;10:48.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology and Cell BiologyUniversity of South Florida Morsani College of MedicineTampaUSA

Personalised recommendations